British journal of anaesthesia
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The process of systematic review has shone a light on the methodology of randomized controlled trials. Notably, a range of potential biases hinders the interpretation of chronic pain trials. These include a consistent bias favouring active over placebo in trials that are small and of short duration. ⋯ They have been small and short, and used inappropriate imputation and outcomes unconnected to the experiences of most patients. While these designs are useful for answering some questions, they may be insensitive for many interventions. Newer designs, like enriched enrolment randomized withdrawal (EERW) trials or clinical effectiveness trials, are potentially more interesting and informative.
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Recent years have witnessed substantially increased research regarding sex differences in pain. The expansive body of literature in this area clearly suggests that men and women differ in their responses to pain, with increased pain sensitivity and risk for clinical pain commonly being observed among women. Also, differences in responsivity to pharmacological and non-pharmacological pain interventions have been observed; however, these effects are not always consistent and appear dependent on treatment type and characteristics of both the pain and the provider. ⋯ Psychosocial processes such as pain coping and early-life exposure to stress may also explain sex differences in pain, in addition to stereotypical gender roles that may contribute to differences in pain expression. Therefore, this review will provide a brief overview of the extant literature examining sex-related differences in clinical and experimental pain, and highlights several biopsychosocial mechanisms implicated in these male-female differences. The future directions of this field of research are discussed with an emphasis aimed towards further elucidation of mechanisms which may inform future efforts to develop sex-specific treatments.
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Chronic pain affects ∼20% of the European population and is commoner in women, older people, and with relative deprivation. Its management in the community remains generally unsatisfactory, partly because of lack of evidence for effective interventions. ⋯ Risk factors include socio-demographic, clinical, psychological, and biological factors. These are relevant to our understanding of chronic pain mechanisms and the nature of, and responses to, current and future treatments.
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Research efforts over the past two decades have helped us better understand the biological mechanisms that lead to chronic pain. Despite this, there has been limited progress in developing novel analgesics to treat sufferers of persistent pain conditions, who may account for as many as one-fifth of the population. ⋯ We review the significant clinical evidence that neuronal activity from the periphery is a major contributor to painful symptom production and that peripheral mediators play a substantial role in this aberrant nociceptor activity. We discuss the clinical benefits of blocking individual known mediators and describe our own approach to identify novel mediators.
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Inflammation is the process by which an organism responds to tissue injury involving both immune cell recruitment and mediator release. Diverse causes of neuropathic pain are associated with excessive inflammation in both the peripheral and central nervous system which may contribute to the initiation and maintenance of persistent pain. Chemical mediators, such as cytokines, chemokines, and lipid mediators, released during an inflammatory response have the undesired effect of sensitizing and stimulating nociceptors, their central synaptic targets or both. ⋯ This review aims to provide an overview of inflammatory mechanisms at differing levels of the sensory neuroaxis with a focus on neuropathic pain. We will compare and contrast neuropathic pain states such as traumatic nerve injury which is associated with a vigorous inflammatory response and chemotherapy induced pain in which the inflammatory response is much more modest. Targeting excessive inflammation in neuropathic pain provides potential therapeutic opportunities and we will discuss some of the opportunities but also the clinical challenges in such an approach.