The journal of pain : official journal of the American Pain Society
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The role of the complement system in pain syndromes has garnered attention on the back of preclinical and clinical evidence supporting its potential as a target for new analgesic pharmacotherapies. Of the components that make up the complement system, component 5a (C5a) and component 3a (C3a) are most strongly and consistently associated with pain. Receptors for C5a are widely found in immune resident cells (microglia, astrocytes, sensory neuron-associated macrophages (sNAMs)) in the central nervous system (CNS) as well as hematogenous immune cells (mast cells, macrophages, T-lymphocytes, etc.). ⋯ A perspective on the optimal application of different C5a inhibitors for different types (e.g., neuropathic, post-surgical and chemotherapy-induced pain, osteoarthritis pain) and stages (e.g., acute, subacute, chronic) of pain is also provided to help guide future clinical trials. PERSPECTIVE: This review highlights the role and mechanisms of complement components and their receptors in physiological and pathological pain. The potential of complement-targeted therapeutics for the treatment of chronic pain is also explored with a focus on C5a inhibitors to help guide future clinical trials.
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Randomized Controlled Trial
Assessing the influence of non-ischaemic A-fiber conduction blockade on offset analgesia: an experimental study.
Offset analgesia (OA) is believed to reflect the efficiency of the endogenous pain modulatory system. However, the underlying mechanisms are still being debated. Previous research suggested both, central and peripheral mechanisms, with the latter involving the influence of specific A-delta-fibers. ⋯ However, further studies are needed to substantiate a central rather than peripheral influence on OA. PERSPECTIVE: This article presents the observation of OA before, during, and after a successful A-fiber conduction blockade in healthy volunteers. A better understanding of the mechanisms of OA and endogenous pain modulation, in general, may help to explain the underlying aspects of pain disorders.
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Individuals with chronic pain report disproportionally higher rates of trauma, yet it is unclear whether different types of trauma (eg, sexual, accidental trauma) are associated with worse pain outcomes. The present study sought to 1) identify subgroups of people with chronic pain based on trauma type, and 2) determine whether subgroups differ in terms of pain characteristics over a 2-year period. Individuals with chronic pain (N = 1,451) participated in an online study and completed self-report questionnaires at baseline, 3-, 12-, and 24-month follow-up. ⋯ The findings underscore the importance of screening for trauma and suggest that the type and variety of trauma experienced may be relevant to pain-related outcomes. PERSPECTIVE: This article highlights how an individual's unique trauma history may be related to their current pain experience. Knowledge of the type and frequency of past trauma may have relevant clinical implications for the treatment of chronic pain.
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The epidemiology and prognosis of radiation-induced chronic pain, especially chronic neuropathic pain (CNP), are the understudied domain among head and neck cancer (HNC) survivors after radiotherapy (RT). This study aimed to estimate the prevalence of such chronic pain, and explore its correlations with mental health, sleep disorders, cognitive function, and quality of life (QOL) within these patients. This research encompassed HNC survivors post RT. ⋯ This study underscores the substantial prevalence of chronic pain, particularly CNP, and its potential impact on the mental health, sleep, and QOL among HNC survivors post RT. PERSPECTIVE: This study highlights the high prevalence of radiation-induced chronic pain and CNP, and their potential impacts on anxiety, depression, sleep, and QOL among the HNC survivors. Clinically, these findings have important implications for improving the care and outcomes of HNC survivors.
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Head and neck squamous cell carcinoma (HNSCC) is painful, and perineural invasion (PNI) has been associated with the worst pain. Pain due to HNSCC is diverse and may vary based on clinicopathological factors. This study aims to characterize different pain patterns linked with PNI, its influence on daily functioning, and gain insights into molecular changes and pathways associated with PNI-related pain in HNSCC patients. ⋯ PERSPECTIVE: PNI independently predicts function-evoked pain. Different pain phenotypes affect daily activities differently. We identified a list of candidate genes involved in the extracellular matrix structure and function that can be targeted for both cancer and cancer pain control.