Pain

Pain is a multifaceted experience that encompasses both sensory-discriminative and emotional components. It ranges from acute nociceptive pain—an adaptive alarm signalling actual or potential tissue damage—to chronic pain, which may persist long after initial healing or arise without any clear peripheral insult. At the most basic level, noxious stimuli are transduced by specialised peripheral nerve endings (nociceptors), transmitted via spinal pathways and modulated by descending brainstem circuits before being perceived in higher centres. Yet perception is shaped as much by mood, belief and past experience as by raw nociceptive input. The biopsychosocial model highlights how genetic predisposition, psychological state and social context interact to amplify or dampen pain. Central sensitisation, in which dorsal-horn and supraspinal neurones become hyperresponsive, can maintain pain in the absence of ongoing peripheral drive. Globally, chronic pain affects an estimated one in five people, drives disability across all age groups and imposes enormous socioeconomic burdens. Improving outcomes therefore demands integrated strategies that combine mechanistic insight, functional rehabilitation and attention to emotional well-being.

Research from Nature Portfolio

A novel study has identified a distinct population of D1-type neurones in the nucleus accumbens that simultaneously governs nociceptive responses and non-rapid eye movement sleep. Selective activation of these neurones promotes both heightened pain-like behaviour and arousal, whereas their inactivation yields analgesia and sleep enhancement. Differential projections from this ensemble to the ventral tegmental area and preoptic sleep-promoting regions confer modality specificity, opening up the prospect of targeting shared circuits to treat co-morbid pain and insomnia.

Work in osteoarthritis has shown that the nerve growth factor receptor Ngfr is upregulated in osteochondral cells and plays a vital role in attenuating inflammation, maintaining bone remodelling signals and preventing accelerated joint damage. Loss of Ngfr in animal models exacerbates inflammatory pathways and disrupts skeletal repair, suggesting that careful modulation of NGF signalling may be required to balance analgesia with tissue integrity.

A Bayesian network meta-analysis of physiotherapeutic and non-conventional interventions for chronic low back pain demonstrates that individually adapted exercise programmes yield the greatest reductions in pain and disability, while multidisciplinary approaches confer superior functional improvements. These findings reinforce the central importance of tailored physical activity and integrative care in musculoskeletal rehabilitation.

Research from all publishers

Advanced imaging protocols have become indispensable in trials of anti-nerve growth factor antibodies for osteoarthritis. High-resolution MRI and weight-bearing radiography are now used to exclude participants at risk of rapid structural progression and to monitor early safety signals, thereby enhancing risk-mitigation strategies without impeding the evaluation of analgesic efficacy.

Experimental studies in healthy volunteers reveal that total sleep deprivation markedly increases sensitivity to thermal and pressure stimuli, impairs endogenous conditioned pain modulation and facilitates temporal summation of pain. These effects underscore the direct impact of sleep loss on central pain-inhibitory pathways and help explain the bidirectional link between insomnia and chronic pain syndromes.

Natural language processing of electronic medical record free text has been used to develop deep-learning models that accurately identify red-flag indicators in patients presenting with low back pain. By capturing risk factors buried in clinical notes, these algorithms support earlier decision-making on imaging and specialist referral, illustrating the promise of AI-driven tools in streamlining pain management pathways.

Pain publication trend

The graph below shows the total number of articles in pain across all publications each year (not limited to Nature Index journals).

Technical terms

Nociceptor: A specialised sensory receptor in peripheral tissues that detects noxious mechanical, thermal or chemical stimuli and initiates pain signalling.

Central sensitisation: A state of increased responsiveness of central neurones to input, characterised by expansion of receptive fields and lowered pain thresholds, contributing to persistent pain.

Conditioned pain modulation (CPM): An endogenous inhibitory mechanism in which one painful stimulus reduces perception of a second noxious input, often assessed experimentally.

Biopsychosocial model: An integrative framework that recognises biological, psychological and social factors as interacting determinants of pain experience and disability.

Neuroplasticity: The capacity of neurones and neural circuits to change structurally and functionally in response to activity, injury or environmental influences, underpinning sensitisation.

Allodynia: Pain elicited by stimuli that do not normally provoke pain, reflecting aberrant central or peripheral processing.

Hyperalgesia: An exaggerated pain response to a stimulus that is normally painful, indicative of peripheral or central sensitisation.

References

1. Pain as a Subjective, Multidimensional Experience.
2. A common neuronal ensemble in nucleus accumbens regulates pain-like behaviour and sleep. Nature Communications (2023).
3. Nerve growth factor receptor limits inflammation to promote remodeling and repair of osteoarthritic joints. Nature Communications (2024).
4. Role of imaging for eligibility and safety of a-NGF clinical trials. Therapeutic Advances in Musculoskeletal Disease (2023).
5. Physiotherapeutic and non-conventional approaches in patients with chronic low-back pain: a level I Bayesian network meta-analysis. Scientific Reports (2024).
6. Total sleep deprivation increases pain sensitivity, impairs conditioned pain modulation and facilitates temporal summation of pain in healthy participants. PLOS ONE (2019).
7. Identifying Risk Factors Associated With Lower Back Pain in Electronic Medical Record Free Text: Deep Learning Approach Using Clinical Note Annotations. JMIR Medical Informatics (2023).