Revolutionising Cellular Regeneration and Longevity With AI

The article “Accelerating life sciences research,” published by OpenAI on 22 August 2025, outlines a significant collaboration between OpenAI and Retro Biosciences aimed at advancing life sciences research through the application of artificial intelligence. The partnership has resulted in the development of GPT-4b micro, a specialised AI model derived from a scaled-down version of OpenAI’s GPT-4o. This model is tailored specifically for protein engineering, a critical area in biotechnology with potential applications in regenerative medicine and therapeutic development.

Development and Capabilities of GPT-4b micro

GPT-4b micro was trained on a comprehensive dataset that includes protein sequences, biological texts, and 3D protein structure data. This training enables the model to generate protein sequences with highly specific properties, such as those containing disordered regions, which are challenging to design due to their lack of fixed structure. The model’s ability to predict and generate such sequences is a significant advancement, as these proteins are often central to biological processes but difficult to engineer using traditional methods.

Focus on Yamanaka Factors

The collaboration focused on optimising the Yamanaka factors—four proteins (OCT4, SOX2, KLF4, and MYC) discovered by Shinya Yamanaka, whose work on induced pluripotent stem cells (iPSCs) earned him the Nobel Prize in Physiology or Medicine in 2012. These proteins are used to reprogram adult cells into iPSCs, which have the potential to develop into any cell type in the body. This reprogramming is a cornerstone of regenerative medicine, with potential applications in treating conditions such as blindness, diabetes, infertility, and organ shortages caused by disease or ageing.

However, the reprogramming process is inherently inefficient, with less than 0.1% of cells successfully converting into iPSCs, and the process can take over three weeks. By leveraging GPT-4b micro, the OpenAI-Retro Biosciences team achieved a remarkable 50-fold increase in the expression of stem cell reprogramming markers, significantly improving the efficiency of the process. This breakthrough could reduce the time and resources needed for iPSC production, bringing regenerative therapies closer to clinical reality.

Implications and Limitations

The article underscores the potential of AI-driven protein engineering to accelerate therapeutic development. By enabling the design of proteins with enhanced functionality, GPT-4b micro could streamline the development of treatments for a range of diseases. However, the article also cautions that the results, while promising, are based on in silico (computer-based) evaluations. Real-world validation through experimental studies is necessary to confirm the practical utility of the generated protein sequences. This step is critical to ensure that the AI-designed proteins perform as expected in biological systems.

Broader Context

The collaboration exemplifies how AI can be integrated into life sciences to address complex biological challenges. By combining OpenAI’s expertise in large-scale AI models with Retro Biosciences’ focus on extending human lifespan through cellular reprogramming, the partnership demonstrates the transformative potential of interdisciplinary approaches. The development of GPT-4b micro also highlights the adaptability of AI models, showing how a general-purpose model like GPT-4o can be fine-tuned for highly specialised tasks in biotechnology.

In summary, the article presents a compelling case for the role of AI in revolutionising life sciences research. The creation of GPT-4b micro and its application to improving Yamanaka factor efficiency mark a significant step forward in protein engineering and regenerative medicine, though further validation is needed to translate these advances into practical therapies.

The Complex Landscape of Pain: Why Our Experiences Differ

I. Introduction: The Enigma of Pain – Setting the Stage
Pain, a seemingly universal experience, presents a profound paradox: while it serves as a vital alarm system, its intensity and impact vary wildly among individuals, even in response to similar injuries. It is a phenomenon that is both deeply personal and globally ubiquitous, prompting a deeper scientific inquiry into its mechanisms and manifestations. The central premise explored in this article, mirroring the focus of the Guardian article from July 13, 2025, is “The fascinating science of pain – and why everyone feels it differently”. This immediately establishes the article’s dual focus: delving into the intricate biological underpinnings of pain and exploring the profound subjective variations in its perception.
A compelling illustration of this paradox is the extraordinary account of John Sattler from the 1970 rugby league grand final. As the leader of the South Sydney Rabbitohs, Sattler entered the match with immense pressure, seeking redemption after his team’s loss in the 1969 final. The opportunity for glory was palpable, and the team was determined to seize it. Early in the game, Sattler sustained a shattered jaw during a tackle, an injury that would typically be incapacitating. Yet, remarkably, he continued to play, completing the grand final despite the severe physical damage. This anecdote powerfully demonstrates that pain is not merely a direct, proportional response to tissue damage. If pain were solely a physical input, such an injury should have immediately rendered him unable to continue. Instead, his ability to perform suggests that pain is not just a sensation received by the brain, but rather an output or construction of the brain itself. The brain appears to determine whether and how much pain to generate based on a multitude of inputs, including the immediate context, the perceived threat, and, crucially, the individual’s motivational state. As the article states, “When it comes to suffering, perspective is everything”. This foundational understanding shifts the focus from a simplistic “where does it hurt?” to a more complex “why does it hurt this way for this person?”, laying the groundwork for exploring the multifaceted influences on pain perception.

II. Pain: More Than Just a Sensation – A Multifaceted Experience
Expanding beyond a simplistic view, pain is formally defined as “an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage.” This definition is critical because it immediately highlights that pain is far more than just a physical sensation, like touch or temperature. It is a complex, subjective experience that inherently involves sensory, emotional, cognitive, and motivational components. Evolutionarily, pain serves a vital protective function, driving individuals to withdraw from harmful stimuli and promoting behaviours that facilitate healing. It is an essential survival mechanism, alerting the body to danger and prompting necessary action.
To fully grasp the intricate nature of pain and its variability, the prevailing framework is the biopsychosocial model. This model posits that pain is not solely a product of biological factors, but rather an emergent phenomenon influenced by a dynamic interplay of biological elements (such as genetics, tissue damage, and neurophysiology), psychological factors (including thoughts, emotions, and coping strategies), and social factors (like cultural background, social support networks, and environmental context). This holistic perspective is indispensable for accounting for the wide spectrum of individual differences observed in pain experiences. The explicit linking of “fascinating science” with “why everyone feels it differently” in the article’s title underscores that a purely biological explanation is insufficient to account for the observed variations. The scientific understanding of pain must therefore encompass not only physiology but also psychology and sociology. The integration of these diverse domains within the biopsychosocial model represents a significant scientific advancement that explains the profound differences in individual pain experiences. This comprehensive view reveals that understanding pain necessitates moving beyond a narrow biomedical lens to appreciate its complex properties arising from the interplay of multiple systems, which is fundamental for developing effective and compassionate pain management strategies.

III. The Biological Underpinnings of Pain Perception
At the core of the biological experience of pain lies nociception, the physiological process by which noxious, or potentially damaging, stimuli are detected. This process involves specialised sensory neurons, known as nociceptors, which are activated by intense mechanical, thermal, or chemical stimuli. These signals are then transmitted to the central nervous system. It is crucial to differentiate nociception, which is the physiological process of detecting and transmitting noxious stimuli, from pain, which is the subjective, conscious experience of discomfort. The journey of a pain signal typically begins at the peripheral nociceptors, travels via the spinal cord, specifically through the dorsal horn, and ascends to various regions within the brain.
The brain’s processing of pain is not confined to a single “pain centre” but rather involves a distributed network often referred to as the “pain matrix.” Key brain regions contribute distinct aspects to the pain experience. The somatosensory cortex is involved in localising the pain and determining its intensity. The insula plays a role in the emotional and interoceptive awareness of pain, contributing to the feeling of “unpleasantness.” The anterior cingulate cortex is implicated in the emotional and cognitive aspects, including the motivational drive to escape pain, while the prefrontal cortex contributes to cognitive modulation, decision-making, and the overall interpretation of the pain experience. This intricate network highlights the profound complexity of pain processing within the central nervous system.
Furthermore, a complex array of neurotransmitters and neuromodulators plays a critical role in facilitating or inhibiting pain signals at different levels of the nervous system. Neurotransmitters like substance P and glutamate facilitate pain transmission, while others, such as GABA, can inhibit it. Neuromodulators, including the body’s endogenous opioids (endorphins), serotonin, and norepinephrine, are crucial components of the body’s intrinsic pain-modulating systems, which can either amplify or dampen pain signals.
Individual pain thresholds and tolerance are also influenced by genetic predispositions. Variations in genes coding for ion channels, opioid receptors, and inflammatory mediators can predispose individuals to different pain sensitivities or even to the development of chronic pain conditions. Conditions related to blood disorders, such as haemophilia, which often involve joint pain, can manifest unique pain experiences due to underlying biological mechanisms. This reinforces the significant role of biological factors in shaping an individual’s pain experience. However, while these biological foundations are crucial components of the “fascinating science of pain” , they are not entirely deterministic. Genetic predispositions or specific biological conditions might influence the capacity for pain, but they do not fully dictate the subjective experience. There is a biological predisposition or capacity for pain, but the actual experience is profoundly modulated by other factors. This sets the stage for understanding the critical interplay between “bottom-up” biological signals and “top-down” psychological and social modulations, explaining why two individuals with similar biological injuries might report vastly different levels of pain.

IV. Psychological and Social Modulators of Pain
Beyond the biological circuitry, psychological and social factors profoundly shape pain perception, demonstrating how the brain’s “perspective” truly comes into play. The individual’s state of mind and their broader social environment exert a powerful top-down influence on how nociceptive signals are processed and ultimately experienced.
Mood and emotion are significant modulators. Conditions such as anxiety, depression, fear, and chronic stress can amplify pain signals, lower pain thresholds, and prolong pain experiences. The brain, when in a state of heightened emotional distress, may interpret incoming signals as more threatening, thereby increasing the perceived intensity of pain. Conversely, positive emotions, a sense of safety, or states of calm can sometimes mitigate pain, demonstrating the reciprocal relationship between emotional well-being and pain perception.
Attention and expectation also play a critical role. When an individual’s attention is focused intently on their pain, its intensity can be amplified. Conversely, distraction, whether through engaging activities or mental exercises, can significantly reduce perceived pain. The placebo and nocebo effects serve as powerful demonstrations of how expectations alone can profoundly alter pain perception. If an individual expects a treatment to relieve pain (placebo), they may experience genuine relief, even if the treatment is inert. Conversely, if they anticipate negative effects (nocebo), their pain may worsen. Past experiences and learning also contribute to an individual’s pain profile. Previous painful encounters, especially traumatic ones, can “prime” the nervous system, leading to heightened sensitivity, a phenomenon known as central sensitisation, where the nervous system becomes overly responsive to pain signals. Furthermore, an individual’s coping strategies significantly influence their pain experience. Active coping mechanisms, such as problem-solving, seeking social support, or engaging in physical activity, can reduce the impact of pain and improve functionality. In contrast, passive coping strategies, like catastrophising (exaggerating the negative aspects of pain) or avoidance behaviours, can exacerbate pain and contribute to chronicity.
The social and cultural fabric surrounding an individual also profoundly influences pain. Cultural norms dictate how pain is expressed, interpreted, and managed. What is considered stoic endurance in one culture might be viewed as excessive suffering or a call for immediate intervention in another. These cultural scripts shape an individual’s willingness to report pain, their coping behaviours, and their expectations of treatment. Social support, or its absence, is another critical factor. Feeling understood, validated, and supported by family, friends, or healthcare providers can significantly reduce distress and enhance coping mechanisms. Conversely, social isolation or a lack of validation can worsen pain and contribute to feelings of helplessness. The broader environmental context, such as being in a safe, supportive hospital environment versus a chaotic or threatening battlefield, can also dramatically alter pain perception, further reinforcing the idea that “perspective is everything”. The brain does not merely receive pain signals; it actively interprets them through the lens of an individual’s psychological state, their past experiences, and their current social environment. This “top-down” modulation can either amplify or diminish the “bottom-up” nociceptive signals originating from tissue damage. This dynamic interplay between mind and body explains why two individuals with identical physical injuries might report vastly different levels of pain, underscoring the necessity of moving beyond purely pharmacological pain treatments towards multidisciplinary approaches that address the whole person, including their mental health and social circumstances.

V. Why Pain is Personal: Exploring Individual Differences
The profound variability in pain experience, captured by the article’s central question of “why everyone feels it differently” , is the culmination of the intricate interplay between biological predispositions, psychological states, and social contexts. Pain is not a simple input-output mechanism but an emergent property of a complex, dynamic system, making each individual’s experience truly unique. The brain integrates all available information – sensory input, past memories, current emotions, future expectations, and social cues – to construct a personal meaning of the pain. This personal meaning then dictates the intensity, unpleasantness, and overall impact of the pain. The John Sattler anecdote, where his brain prioritised the goal of winning over the raw nociceptive input from a shattered jaw , perfectly illustrates this capacity for the brain to construct an experience based on overarching goals and context.
Consider two hypothetical scenarios that highlight these divergent pain experiences:
* Scenario 1: Two individuals present with identical lower back disc herniations, confirmed by imaging. One, a highly anxious person with a history of trauma and limited social support, experiences debilitating, chronic pain that significantly impairs their daily life. Their pain is amplified by fear of movement, catastrophising thoughts, and a sense of helplessness. The other individual, an optimistic person with strong social support, effective coping strategies, and a positive outlook, experiences manageable, acute pain that resolves relatively quickly with targeted physical therapy. Despite identical physical injuries, their pain journeys are vastly different due to their psychological and social landscapes.
* Scenario 2: A child experiences a minor scrape on their knee, while an adult sustains a similar superficial injury. The child’s pain might be amplified by fear, a lack of understanding of the injury’s benign nature, and a desire for comfort, leading to intense crying and distress. The adult, drawing on past experiences and learned stoicism, might downplay the pain, quickly apply a plaster, and continue with their activities, perceiving it as a minor inconvenience.
To further clarify the nuances of individual pain, it is helpful to distinguish between pain threshold and pain tolerance. Pain threshold refers to the minimum intensity of a noxious stimulus that is perceived as painful. This is largely a physiological measure, indicating the point at which nociceptors are activated and signals reach conscious awareness. In contrast, pain tolerance is the maximum intensity or duration of pain that a person is willing or able to endure before withdrawing or seeking relief. Pain tolerance is highly subjective and significantly influenced by psychological and social factors, such as motivation, emotional state, cultural background, and prior experiences. This distinction helps to explain why people “feel it differently” – while their pain thresholds might be similar, their tolerance for enduring that pain can vary widely.

VI. Implications for Pain Management and Empathy
A deeper understanding of pain’s inherent individuality is fundamentally transforming pain management, moving away from a simplistic “one-size-fits-all” approach towards more personalised, multidisciplinary strategies. Effective pain assessment now extends beyond merely identifying physical symptoms to comprehensively evaluating psychological distress, social circumstances, and individual coping styles. This holistic approach recognises that treating pain effectively requires addressing the whole person, not just the physical injury. Consequently, modern pain management often integrates pharmacological treatments with a range of non-pharmacological therapies, including psychological interventions such as Cognitive Behavioural Therapy (CBT) and Acceptance and Commitment Therapy (ACT), physical therapy, and social interventions aimed at improving support networks and environmental factors.
Given the subjective nature of pain, the crucial role of empathy and validation in clinical settings and everyday interactions cannot be overstated. Because pain is a personal construction, validating an individual’s experience, even when objective physical findings are minimal or disproportionate to the reported pain, is paramount for building trust and facilitating recovery. Dismissing someone’s pain, for instance, by suggesting “it’s all in your head,” can exacerbate distress, erode trust in healthcare providers, and ultimately hinder effective treatment. Such dismissal invalidates the individual’s lived experience, which is a real and impactful phenomenon, regardless of its underlying physical pathology.
Furthermore, a better understanding of the complex aetiology of pain can help address the significant societal challenge of invisible pain, such as chronic back pain or fibromyalgia. These conditions often lack clear objective markers, leading to skepticism and stigma. By acknowledging that pain is a complex output of the brain influenced by a multitude of biological, psychological, and social factors, society can move towards reducing this stigma and fostering greater support for those affected. The scientific insights into pain’s multidimensionality directly lead to the necessity of a holistic, patient-centred approach to pain management. This means moving beyond solely treating the “injury” to treating the “person” experiencing the pain. Moreover, the subjective nature of pain necessitates a fundamental shift towards greater empathy and validation, particularly for chronic conditions where physical pathology may not fully explain the reported pain. This understanding bridges the gap between theoretical scientific knowledge and its real-world application, advocating for more effective, humane, and patient-centred pain care.

VII. Conclusion: Towards a Holistic Understanding of Pain
The exploration of pain reveals it to be a complex, dynamic, and profoundly personal experience, shaped by an intricate interplay of biological, psychological, and social factors. The “fascinating science” of pain lies precisely in unravelling this complexity and comprehending why “everyone feels it differently”. It is not merely a signal of tissue damage but a sophisticated output of the brain, influenced by a myriad of internal and external cues.
Circling back to the compelling case of John Sattler, whose ability to play a grand final with a shattered jaw highlighted that “When it comes to suffering, perspective is everything”. This perspective is not merely a mental state; it is an emergent property of the entire biopsychosocial system, where motivation, context, and the brain’s interpretation of threat and reward can profoundly alter the experience of pain.
Ongoing research in pain science, including advancements in neuroimaging, genetic studies, and the development of integrated care models, continues to deepen our understanding of this multifaceted phenomenon. This evolving knowledge holds broader societal significance, informing healthcare policy, promoting public education, and fostering a more compassionate and nuanced approach to pain in daily life. Ultimately, the journey into the science of pain reveals not just the mechanics of discomfort, but the remarkable adaptability, resilience, and inherent complexity of the human experience itself. This scientific understanding empowers both individuals experiencing pain and those who provide care for them, paving the way for more effective and empathetic support.

Manage Longstanding Low Back Pain by Spending Time in Nature

Study Overview

The article “Being away from everything”: Exploring the importance of access to nature for individuals living with chronic low back pain, published in the Journal of Pain, investigates how nature can aid in managing chronic low back pain (cLBP). It involved ten semi-structured interviews with people averaging 50.1 years old and living with cLBP for about 19.1 years.

Key Findings

The study found that nature can provide distraction, reduce isolation, and offer a calming environment, enhancing pain self-management. However, many face challenges like physical disabilities, environmental hazards, or lack of proximity to natural spaces. It suggests integrating nature-based activities into treatment plans and exploring virtual reality for those unable to access nature.

Detailed Analysis and Background

The article presents a pioneering qualitative cross-sectional study focused on understanding the role of natural environments in managing chronic low back pain (cLBP). The study, conducted and published in June 2025, addresses the growing evidence against the effectiveness of ‘one-size-fits-all’ pharmacological approaches, advocating for alternative non-pharmacological therapies such as green social prescribing and spending time in nature.

Methodology and Participants

The research methodology involved ten semi-structured interviews, primarily with women (9 out of 10 participants), with an average age of 50.1 years and an average duration of living with cLBP of 19.1 years. This qualitative approach aimed to explore the lived experiences of individuals, providing deep insights into their coping strategies and the role of nature in ameliorating pain. The analysis was conducted using Reflexive Thematic Analysis, identifying two main themes: (1) Importance of Nature and (2) Inaccessible Nature, each with four subthemes respectively.

Key Findings and Themes

The theme “Importance of Nature” underscores the benefits of accessing natural environments, which can significantly aid in self-management of cLBP. Participants reported that being in nature offered distraction, reduced feelings of isolation, and provided a calming environment, which helped alleviate pain and improve mental well-being. For instance, those able to immerse themselves in larger green spaces, such as forests, felt more positive, as they could lose themselves in the environment and focus less on their pain levels.

However, the theme “Inaccessible Nature” revealed significant barriers, including physical disabilities, environmental obstacles or hazards, and geographical limitations. These challenges often undermined the ability to access nature, highlighting an unmet clinical need. The study emphasizes that many individuals encounter substantial obstacles, such as uneven terrain, limited seating, or difficulties leaving their homes, making it challenging to benefit from the restorative properties of nature.

Implications and Recommendations

The findings suggest that integrating nature-based activities into treatment plans could be beneficial, offering a promising avenue for improving overall well-being for those with cLBP. The researchers recommend exploring virtual reality interventions to simulate nature experiences for those unable to access outdoor spaces, addressing accessibility issues. This approach could help make the benefits of nature accessible to everyone, potentially through technological innovations. Simple changes, such as better paths and seating, were also suggested to enhance real-world access.

The study marks the first qualitative investigation focusing directly on the nuanced role of natural settings within the coping mechanisms employed by people with cLBP. This pioneering aspect underscores the need for further research into how nature can be incorporated into holistic and multidisciplinary frameworks for treating pain, aligning with leading international organizations’ recommendations.

Contextual Background

Chronic low back pain is a major public health issue, with the highest prevalence globally among musculoskeletal conditions and being the leading cause of disability worldwide. It affects individuals of all ages, with peak cases at 50–55 years, and women experiencing it more frequently. The condition often leads to work loss, participation restriction, and reduced quality of life, making innovative approaches like nature-based interventions particularly relevant.

The study’s emphasis on accessibility challenges also aligns with broader discussions on health equity, addressing significant physical barriers faced by people living with chronic pain, as highlighted in the University of Plymouth news release. This includes the need for better infrastructure, such as improved paths and seating, to facilitate access to natural spaces.

Conclusion

In conclusion, the article provides valuable insights into the therapeutic potential of nature for individuals with cLBP, while also highlighting significant accessibility barriers. It advocates for innovative solutions like virtual reality to bridge these gaps, contributing to the broader discourse on holistic pain management. The findings are particularly timely, given the current understanding of cLBP as a major global health challenge, and offer a foundation for future research into nature-based interventions.

New Hope For Joint Repair

A recent scientific breakthrough by Chen at al. could significantly improve how we treat cartilage damage — a common problem in joints like knees and hips that often leads to long-term pain and arthritis.

Cartilage is notoriously slow to heal, largely because its cells (called chondrocytes) have limited access to energy. To tackle this, researchers have developed a new technique that enhances the energy levels of these cells, helping them function better and regenerate damaged tissue more effectively.

The research team created energy-enhanced exosomes — tiny vesicles called Suc-EXO — which are loaded with high levels of ATP, the molecule that powers cell activity. When these Suc-EXO were delivered to stem cells and cartilage cells, they boosted energy metabolism and activated key repair pathways.

In particular, the treatment improved the transformation of stem cells into cartilage-producing cells and helped existing cartilage cells maintain their function by supporting healthy mitochondria (the cell’s energy centres).

Tests in a rabbit model with cartilage injuries showed that Suc-EXO, when delivered via a gel, significantly improved cartilage regeneration. The repaired tissue had higher levels of collagen type II and aggrecan — essential components of strong, healthy cartilage.

This innovative “organelle-tuning” approach opens up a new avenue for regenerative therapies and could one day lead to more effective treatments for joint injuries and osteoarthritis.

Chronic Low Back Pain, Bacterial Infection, and Antibiotic Treatment

Chronic low back pain (CLBP) is a leading cause of disability globally, affecting millions and posing significant challenges to healthcare systems due to its complex aetiology and limited effective treatments (Gilligan et al., 2021). Recent research has sparked debate by suggesting that low-grade bacterial infections, particularly involving Cutibacterium acnes (C. acnes), may contribute to CLBP in a subset of patients, especially those with disc herniation and Modic Type 1 changes (bone oedema visible on MRI). This hypothesis, if validated, could revolutionise treatment by introducing antibiotics as an alternative to conventional therapies or invasive procedures like spinal surgery. However, the evidence remains controversial, with concerns about contamination, antibiotic efficacy, and stewardship. The following summary synthesises findings from key studies, highlighting microbiology evidence, clinical trial outcomes, and ongoing research challenges.

Microbiology Evidence: Bacterial Presence in Herniated Discs

Several studies have investigated whether bacteria, particularly C. acnes, are present in herniated disc tissue and contribute to CLBP. Gilligan et al. (2021) reviewed five well-designed microbiology studies that confirmed bacteria in disc samples, suggesting infection rather than contamination. These studies found C. acnes, a low-virulence anaerobic bacterium commonly associated with acne, in herniated disc tissue, particularly in patients with Modic Type 1 changes. However, the bacterial burden was low, potentially below detection limits in some studies, which may explain conflicting results where bacteria were absent or attributed to surgical contamination (Gilligan et al., 2021).

Astur et al. (2023) conducted a prospective cohort study to identify bacteria in herniated intervertebral discs, reporting C. acnes in a significant proportion of samples. Their stringent aseptic protocols minimised contamination risks, supporting the infection hypothesis. Similarly, Urquhart et al. (2015) conducted a systematic review and found moderate evidence that low-virulence bacteria are present in spinal disc material, particularly in patients with disc herniation and Modic Type 1 changes. They applied Bradford Hill’s criteria to assess causation, concluding modest evidence for a causal link but noting the need for further research to distinguish infection from contamination (Urquhart et al., 2015).

In contrast, Monge-García et al. (2024) explored whether bacterial presence in disc cultures represents true infection or contamination. Their study suggested that while C. acnes was frequently detected, contamination during surgical procedures could not be ruled out, particularly given the bacterium’s ubiquity on skin and in hair follicles. This raises a critical question: are bacteria in disc tissue causative agents of CLBP or incidental findings due to procedural artefacts? The conflicting findings underscore the need for standardised microbiological methods and larger sample sizes to clarify the role of C. acnes (Monge-García et al., 2024).

Clinical Evidence: Antibiotic Efficacy in CLBP

Clinical trials have tested whether antibiotics can reduce pain and disability in CLBP patients with suspected bacterial infections. Two randomised controlled trials (RCTs) reviewed by Gilligan et al. (2021) demonstrated significant pain and disability reductions in patients with CLBP and Modic Type 1 changes treated with oral antibiotics, typically amoxicillin-clavulanate, for up to 100 days. These patients, often unresponsive to conventional treatments like physiotherapy or analgesics, showed clinically meaningful improvements, suggesting antibiotics as a potential alternative to surgery for those facing disc replacement or fusion (Gilligan et al., 2021).

A landmark RCT by Albert et al. (2013), cited across multiple articles, found that 100 days of amoxicillin-clavulanate significantly reduced pain and disability in patients with CLBP post-disc herniation and Modic Type 1 changes compared to placebo. At one-year follow-up, the antibiotic group reported a median Roland Morris Disability Questionnaire (RMDQ) score reduction from 15 to 7, compared to 15 to 14 in the placebo group (p=0.0001). Pain scores and constant pain prevalence also improved significantly (Urquhart et al., 2015; Gilligan et al., 2021). However, the trial reported high rates of adverse events, particularly gastrointestinal issues like diarrhoea, in 65% of the antibiotic group versus 23% in the placebo group, raising concerns about tolerability (Urquhart et al., 2015).

Despite these promising results, not all studies support antibiotic efficacy. Some trials reported modest or non-significant effects, potentially due to underdosing or variable bacterial susceptibility. A review by Czaplewski et al. (2023) highlighted that oral amoxicillin doses (500–1000 mg, two or three times daily) may not achieve adequate intradiscal concentrations to target C. acnes effectively, with only 6.5% of serum concentrations reaching herniated disc tissue. Higher doses (e.g., 1000 mg three times daily) may be needed to reach efficacy targets for 90% of C. acnes strains, suggesting that previous studies may have been underdosed (Czaplewski et al., 2023).

Modic Changes and Infection Hypothesis

Modic Type 1 changes, characterised by vertebral bone oedema, are six times more prevalent in CLBP patients than the general population and are strongly associated with the infection hypothesis. Aebi (2013) noted that 80% of discs infected with C. acnes in surgical samples developed Modic Type 1 changes, suggesting that bacterial infection may trigger inflammation and oedema in adjacent vertebrae (Aebi, 2013). The neovascularisation following disc herniation is thought to allow C. acnes to enter the disc during transient bacteraemia, such as during tooth brushing, leading to chronic low-grade infection (Urquhart et al., 2015).

However, Modic changes may also result from mechanical stress or degeneration, complicating the attribution to infection alone. Lings (2013) and Rolfsen et al. (2024) emphasised that Modic Type 1 and Type 2 changes might represent different stages of a common degenerative process, questioning the specificity of infection as a cause. Rolfsen et al. (2024) proposed a multicentre case-control biopsy study to further investigate bacterial growth in CLBP patients with Modic changes, aiming to use advanced microbiological techniques like PCR to detect low-burden infections and control for contamination (Rolfsen et al., 2024).

Controversies and Challenges

The hypothesis that bacterial infection causes CLBP faces several challenges. First, the presence of C. acnes in disc tissue may reflect contamination rather than infection, given its prevalence on skin and difficulty in culturing due to its anaerobic nature (Monge-García et al., 2024). Second, the clinical significance of antibiotic benefits is debated, with some studies showing only modest effects and high adverse event rates (Gilligan et al., 2021). Third, long-term antibiotic use raises concerns about antimicrobial resistance and secondary infections like Clostridium difficile (Urquhart et al., 2015).

Antibiotic stewardship is a critical issue. The prolonged regimens (up to 100 days) used in trials contrast with typical short-course antibiotic treatments, increasing risks of resistance and side effects. Aebi (2013) and Lings (2013) cautioned against widespread antibiotic use without robust evidence, drawing parallels with the paradigm shift in peptic ulcer treatment following Helicobacter pylori discovery but urging caution until confirmatory studies are conducted.

Future Directions

The reviewed studies advocate for further research to refine patient selection, optimise antibiotic regimens, and address stewardship concerns. Rolfsen et al. (2024) and Czaplewski et al. (2023) emphasised the need for studies incorporating advanced diagnostics (e.g., quantitative microbiology, proteomics) and pharmacokinetic/pharmacodynamic evaluations to ensure adequate intradiscal antibiotic concentrations. Identifying biomarkers, such as cytokine patterns or genetic predispositions, could help select patients most likely to benefit from antibiotics (Gilligan et al., 2021).

Moreover, alternative delivery methods, such as intradiscal antibiotic injections (e.g., PP353, a novel treatment combining linezolid and a thermosensitive gel), are being explored to minimise systemic side effects and improve efficacy (Tripathi et al., 2025, cited in The Guardian). These approaches could offer targeted treatment for infection-related CLBP, reducing the need for prolonged oral antibiotics.

Conclusion

The hypothesis that low-grade bacterial infections contribute to CLBP, particularly in patients with disc herniation and Modic Type 1 changes, is supported by microbiological evidence and some clinical trials demonstrating antibiotic efficacy. However, controversies persist regarding contamination, variable clinical outcomes, and antibiotic stewardship. While antibiotics offer a potential alternative to surgery for a subset of CLBP patients, widespread adoption requires further validation through rigorous, multicentre studies. Future research should focus on optimising diagnostics, treatment regimens, and patient selection to balance efficacy with safety, potentially transforming the management of this debilitating condition.

Antibiotics For Low Back Pain?

Persica Pharmaceuticals has developed PP353, an intradiscal injection designed to treat chronic low back pain linked to bacterial infections, particularly cases associated with Modic changes (pathological alterations in vertebrae seen on MRI). PP353 combines:

• Linezolid (antibiotic) – targets bacterial infection
• Iohexol (contrast agent) – aids imaging and distribution
• Thermosensitive gel – ensures controlled release

Recent Study & Findings

• Conducted on 44 patients
• Patients received two injections four days apart
• 60% reported significant pain and disability reduction
• Study supports infectious origins in some chronic back pain cases

Potential Impact

• Could benefit the 25% of chronic low back pain cases linked to bacterial infection
• Offers a minimally invasive alternative to surgery or long-term medication
• Further clinical trials required before widespread use

Cold Water Immersion and Health

A recent systematic review and meta-analysis published in PLOS ONE aimed to evaluate the psychological, cognitive, and physiological effects of cold-water immersion (CWI) in healthy adults. The study synthesised data from 11 randomised controlled trials encompassing 3,177 participants who engaged in CWI through methods such as cold showers, ice baths, or plunges in water temperatures at or below 15°C for durations of at least 30 seconds. 

Key Findings:

• Inflammation: The analysis revealed that CWI might reduce inflammation. This anti-inflammatory effect is particularly noted in athletic populations, where CWI is often utilised to mitigate exercise-induced muscle soreness. It is with noting that the anti-inflammatory effect may blunt the athlete’s adaption to exercise.
• Stress Reduction: While immediate reductions in stress levels were not observed post-immersion, a significant decrease in stress was reported 12 hours after CWI sessions. This delayed effect suggests that CWI may influence stress-related pathways over time, contributing to improved mental well-being. 
• Immune Function: Regular exposure to cold showers was associated with a reduction in self-reported sickness absence from work. Participants who incorporated daily cold showers into their routines reported fewer instances of illness-related absences, indicating a potential enhancement of immune resilience. 
• Quality of Life and Sleep: Short-term improvements in sleep quality and overall well-being were reported by participants following consistent CWI practices. However, these positive effects appeared to diminish after a period of 90 days, suggesting that the benefits of CWI on sleep and well-being may be transient and possibly require sustained or varied interventions to maintain.

Conclusion:

The study indicates that CWI may offer certain health benefits, particularly in stress reduction and immune function over time. However, the evidence is inconsistent, and many studies are limited by small sample sizes or a focus on athletic populations. Further comprehensive research is needed to fully understand the benefits and effects of cold-water immersion on health. 

Processed Meats Increase Risk of Dementia

A recent study published in Neurology on 11 February 2025, led by researchers from Brigham and Women’s Hospital, has investigated the relationship between long-term red meat consumption and the risk of dementia and cognitive decline in U.S. adults. The study utilised data from the Nurses’ Health Study and the Health Professionals Follow-Up Study, encompassing approximately 170,000 participants over a 43-year period. 

Key Findings:

• Processed Red Meat and Dementia Risk: Individuals with the highest intake of processed red meats—such as bacon, sausages, and hot dogs—exhibited a 13% higher risk of developing dementia compared to those with lower consumption levels.
• Cognitive Decline: High consumption of processed red meats was associated with a 14% increase in subjective cognitive decline, indicating a perceived worsening of cognitive abilities over time.
• Unprocessed Red Meat: The study found that unprocessed red meats, such as beef, lamb, and pork, also contributed to cognitive risks, potentially due to harmful substances like nitrates, sodium, and saturated fats present in these meats.

Mechanisms Behind the Findings:

The detrimental effects of processed red meats on cognitive health are believed to be linked to several factors:

• Nitrates and Nitrites: Commonly used as preservatives in processed meats, these compounds can form nitrosamines, which have been implicated in neurodegenerative processes.
• High Sodium Content: Elevated sodium levels can lead to hypertension, a known risk factor for vascular dementia.
• Saturated Fats: High levels of saturated fats in processed meats are associated with cardiovascular diseases, which can indirectly affect brain health.

Dietary Recommendations:

Based on the findings, the researchers suggest several dietary modifications to mitigate dementia risk:

• Reduce Processed Red Meat Intake: Limiting the consumption of processed meats can lower the risk of cognitive decline.
• Substitute with Healthier Protein Sources: Replacing processed red meats with alternatives such as fish, poultry, nuts, and legumes has been associated with a reduced risk of dementia. For instance, substituting processed red meat with fish was linked to a 28% reduction in dementia risk.
• Adopt Brain-Healthy Diets: Diets like the Mediterranean, DASH, and MIND diets, which are low in red meat and rich in fruits, vegetables, whole grains, and healthy fats, have been associated with decreased dementia risks.

Conclusion:

This extensive study underscores the importance of dietary choices in maintaining cognitive health. Limiting the intake of processed red meats and opting for healthier protein sources may significantly reduce the risk of dementia and support long-term cognitive function.

Food Choices Affect Pain

Introduction

Chronic pain is a widespread issue that significantly impacts quality of life and healthcare systems. While obesity is a well-documented risk factor for chronic pain, recent evidence suggests that other factors, such as diet quality, may also play a role. A recent study explores the relationship between diet quality and body pain in adults, regardless of their levels of adiposity (body fat).

Objective

The primary aim was to investigate whether better diet quality is linked to lower levels of body pain in adults and whether this association remains significant independent of adiposity.

Methods

The research used data from the Whyalla Intergenerational Study of Health, which includes a diverse sample of adults from Whyalla, South Australia. Participants completed detailed assessments, including:

• Diet quality evaluation: Using the Australian Recommended Food Score (ARFS), which measures adherence to dietary guidelines.
• Body pain measurement: Using validated self-reported questionnaires that assess the severity and frequency of pain across the body.
• Adiposity indicators: These included body mass index (BMI), waist circumference, and body fat percentage.
  The study also controlled for confounding factors such as age, sex, physical activity, smoking status, and socio-economic status.

Key Findings

1. Diet Quality and Pain:
   • Higher ARFS scores, indicating better diet quality, were significantly associated with reduced levels of body pain.
   • The association was consistent across various demographic and lifestyle groups.
2. Independence from Adiposity:
   • While higher adiposity was associated with increased body pain, the relationship between diet quality and pain remained significant even after adjusting for adiposity measures.
   • This suggests that diet quality has an independent role in pain modulation.
3. Potential Mechanisms:
   • Nutritional components such as anti-inflammatory foods, antioxidants, and omega-3 fatty acids might contribute to reduced systemic inflammation and pain perception.
   • Conversely, poor diet quality may exacerbate pain through increased inflammation and metabolic dysregulation.

Implications

The findings highlight the importance of a high-quality diet in managing body pain, regardless of body fat levels. This has potential implications for public health strategies and clinical interventions aimed at reducing chronic pain prevalence.

• For individuals: Encouraging adherence to dietary guidelines may help alleviate body pain alongside other health benefits.
• For policymakers and healthcare providers: Integrating dietary advice into pain management protocols could improve patient outcomes.

Conclusion

The study concludes that better diet quality is associated with reduced body pain in adults, and this relationship is independent of adiposity. These results underscore the importance of dietary quality as a modifiable factor in chronic pain prevention and management. Further research is needed to explore specific dietary components and their mechanisms in influencing pain pathways.

This research supports the broader understanding that nutrition plays a critical role in overall health and highlights diet quality as a key factor in pain management strategies.

Changes in Gait, Balance and Strength with Aging

The recent article “Age-related changes in gait, balance, and strength parameters: A cross-sectional study” published in PLOS One by Rezaei et al. examines the impact of aging on various physical performance measures such as gait (walking patterns), balance, and muscular strength. The study employs a cross-sectional design, meaning it analyses data collected at one specific point in time across a diverse sample of adults ranging in age, with the objective of understanding how these physical parameters change as people grow older.

Background and Motivation

The motivation behind this study stems from the known correlation between age-related declines in physical abilities and increased risk of falls, decreased independence, and overall diminished quality of life. As gait, balance, and strength are crucial to maintaining mobility and preventing falls, identifying when and how these factors decline can inform interventions that help older adults retain their independence longer. The study also aims to provide insights for clinicians and healthcare professionals to tailor preventative measures and rehabilitation strategies according to age-specific needs.

Methods

The researchers recruited a large group of participants spanning various age groups and used a range of objective measurements to assess gait, balance, and strength. For gait analysis, the study evaluated variables such as walking speed, stride length, and step time variability. Balance was measured through static and dynamic assessments, which included tests for single-leg standing time and balance stability during movement. Strength was assessed primarily through grip strength and lower limb muscle power tests, which are widely accepted indicators of general muscular strength in ageing populations.

Findings

The study found significant age-related declines across all parameters, with notable differences between age groups:

1. Gait: There was a clear trend of reduced walking speed and shorter stride length with increasing age, coupled with an increase in gait variability. These changes often started to manifest in middle-aged adults and progressively worsened in older age groups.
2. Balance: Balance deficits were observed as early as middle age, with a marked reduction in single-leg standing time and stability during dynamic movements in older adults. The results highlight that both static and dynamic balance abilities diminish with age, increasing the risk of falls.
3. Strength: Muscle strength, particularly grip strength and lower limb power, also showed a steady decline with age. This decline was particularly significant in participants over 60 years, indicating that muscle weakness becomes more prominent and impactful in later years.

Interpretation and Implications

The findings suggest that the aging process is associated with measurable declines in gait, balance, and strength, which collectively heighten the risk of falls and mobility impairments. The study highlights that these changes do not occur suddenly but rather develop gradually, implying that early interventions in middle-aged adults could be beneficial. The researchers suggest that routine assessment of gait, balance, and strength could be integrated into clinical practice to detect early declines and support proactive management strategies.

Conclusion

In summary, this cross-sectional study provides valuable insights into how age impacts physical performance parameters crucial for mobility and independence. The age-related deterioration in gait, balance, and strength underlines the importance of early assessment and targeted exercise or rehabilitation interventions aimed at mitigating these declines. By identifying the specific onset of these changes, healthcare providers can better design preventative programs tailored to the needs of ageing adults, thereby potentially enhancing quality of life and reducing the social and economic burdens associated with falls and functional impairments in the elderly population.

This study reinforces the significance of personalised health strategies and preventive measures in addressing the age-related decline in physical function, advocating for policies that encourage physical activity and strength maintenance from a younger age.