Pain hypersensitivity mechanisms at a glance

Gangadharan, Vijayan; Kuner, Rohini

doi:10.1242/dmm.011502

Cited by 148 publications

(137 citation statements)

References 70 publications

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“…Although the review indicated that many of the changes that occur in the spinal cord result from alterations in the function of dorsal horn interneurons, there was little discussion of the incredible heterogeneity of the interneurons. The present review has the interneurons as its focus, hopefully building upon several excellent reviews that appeared in the last few years (Ribeiro-da-Silva and De Koninck, 2009; Todd, 2010) and others that detailed the incredible biochemical complexity of dorsal horn organization (Gangadharan and Kuner, 2013). …”

Section: Introductionmentioning

confidence: 99%

Transmitting Pain and Itch Messages: A Contemporary View of the Spinal Cord Circuits that Generate Gate Control

Bráz

Solórzano

Wang

et al. 2014

Neuron

367

286

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The original formulation of Gate Control Theory (GCT) proposed that the perception of pain produced by spinal cord signaling to the brain depends on a balance of activity generated in large (non-nociceptive) and small (nociceptive) diameter primary afferent fibers. GCT proposed that activation of the large diameter afferent “closes” the gate by engaging a superficial dorsal horn interneuron that inhibits projection neuron firing. Activation of the nociceptors “opens” the gate through concomitant excitation of projection neurons and inhibition of inhibitory interneurons. Sixty years after publication of the GCT, we are faced with an ever-growing list of morphologically and neurochemically distinct spinal cord interneurons. This review highlights the complexity of superficial dorsal horn circuitry and addresses whether the premises outlined in GCT still have relevance today. By examining the dorsal horn circuits underlying the transmission of “pain” and “itch” messages, we also address the extent to which labeled lines can be incorporated into a contemporary view of GCT.

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Section: Introductionmentioning

confidence: 99%

Transmitting Pain and Itch Messages: A Contemporary View of the Spinal Cord Circuits that Generate Gate Control

Bráz

Solórzano

Wang

et al. 2014

Neuron

367

286

View full text Add to dashboard Cite

show abstract

“…Neuropathic pain is brought about by damage to the nerves themselves and can be as a result of injury, disease, or environmental factors. The boundaries of nociceptive and neuropathic pain overlap and in such instances patients may suffer from pain derived from damage to both tissues and nerves (Gangadharan and Kuner, 2013).…”

Section: Painmentioning

confidence: 99%

Cathepsin S: therapeutic, diagnostic, and prognostic potential

Wilkinson

Williams

Scott

et al. 2015

Biological Chemistry

174

139

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Cathepsin S is a member of the cysteine cathepsin protease family. It is a lysosomal protease which can promote degradation of damaged or unwanted proteins in the endo-lysosomal pathway. Additionally, it has more specific roles such as MHC class II antigen presentation, where it is important in the degradation of the invariant chain. Unsurprisingly, mis-regulation has implicated cathepsin S in a variety of pathological processes including arthritis, cancer, and cardiovascular disease, where it becomes secreted and can act on extracellular substrates. In comparison to many other cysteine cathepsin family members, cathepsin S has uniquely restricted tissue expression and is more stable at a neutral pH, which supports its involvement and importance in localised disease microenvironments. In this review, we examine the known involvement of cathepsin S in disease, particularly with respect to recent work indicating its role in mediating pain, diabetes, and cystic fibrosis. We provide an overview of current literature with regards cathepsin S as a therapeutic target, as well as its role and potential as a predictive diagnostic and/or prognostic marker in these diseases.

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“…The impulses in the nociceptors are conveyed to second order neurons in the spinal medulla 54–56. At spinal level, the signal may be modulated, either amplified or attenuated, by different interneuronal pathways.…”

Section: Introductionmentioning

confidence: 99%

Chronic musculoskeletal pain: review of mechanisms and biochemical biomarkers as assessed by the microdialysis technique

Gerdle¹,

Ghafouri²,

Ernberg³

et al. 2014

JPR

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Chronic musculoskeletal pain conditions are multifaceted, and approximately 20% of the adult population lives with severe chronic pain, with a higher prevalence in women and in lower income groups. Chronic pain is influenced by and interacts with physical, emotional, psychological, and social factors, and a biopsychosocial framework is increasingly applied in clinical practice. However, there is still a lack of assessment procedures based on the activated neurobiological pain mechanisms (ie, the biological part of the biopsychosocial model of pain), which may be a necessary step for further optimizing outcomes after treatments for patients with chronic pain. It has been suggested that chronic pain conditions are mainly driven by alterations in the central nervous system with little or no peripheral stimuli or nociception. In contrast, other authors argue that such central alterations are driven by peripheral alterations and nociceptive input. Microdialysis is an in vivo method for studying local tissue alterations and allows for sampling of substances in the interstitium of the muscle, where nociceptor free nerve endings are found close to the muscle fibers. The extracellular matrix plays a key role in physiologic functions of cells, including the primary afferent nociceptor. The present review mainly concerns the results of microdialysis studies and how they can contribute to the understanding of activated peripheral nociceptive and pain mechanisms in humans with chronic pain. The primary aim was to review molecular studies using microdialysis for the investigation of human chronic muscle pain, ie, chronic masticatory muscle pain, chronic trapezius myalgia, chronic whiplash-associated disorders, and chronic widespread pain/fibromyalgia syndrome. Several studies clearly showed elevated levels of serotonin, glutamate, lactate, and pyruvate in localized chronic myalgias and may be potential biomarkers. These results indicate that peripheral muscle alterations are parts of the activated pain mechanisms in common chronic pain conditions. Muscle alterations have been reported in fibromyalgia syndrome and chronic widespread pain, but more studies are needed before definite conclusions can be drawn. For other substances, results are inconclusive across studies and patient groups.

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Pain hypersensitivity mechanisms at a glance

Cited by 148 publications

References 70 publications

Transmitting Pain and Itch Messages: A Contemporary View of the Spinal Cord Circuits that Generate Gate Control

Transmitting Pain and Itch Messages: A Contemporary View of the Spinal Cord Circuits that Generate Gate Control

Cathepsin S: therapeutic, diagnostic, and prognostic potential

Chronic musculoskeletal pain: review of mechanisms and biochemical biomarkers as assessed by the microdialysis technique

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