Pain
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Chronic neuropathic pain is often a severe and inadequately treated consequence of spinal cord injury (SCI). Recent findings suggest that SCI pain is promoted by spontaneous activity (SA) generated chronically in cell bodies of primary nociceptors in dorsal root ganglia (DRG). Many nociceptors express transient receptor potential V1 (TRPV1) channels, and in a preceding study most dissociated DRG neurons exhibiting SA were excited by the TRPV1 activator, capsaicin. ⋯ TRPV1 knockdown also decreased the incidence of SA in dissociated nociceptors after SCI. Prolonged application of very low concentrations of capsaicin produced nondesensitizing firing similar to SA, and this effect was enhanced by prior SCI. These results show that TRPV1 makes important contributions to pain-related hypersensitivity long after SCI, and suggest a role for TRPV1-dependent enhancement of nociceptor SA that offers a promising target for treating chronic pain after SCI.
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Little is known about the central mechanisms underlying the transition from local or regional to widespread pain in low back pain patients. The aim of the study was to find out if muscle input induced by injection of nerve growth factor (NGF) can be used as an animal model for studying spinal mechanisms involved in widespread myofascial low back pain. Electrophysiological recordings from rat dorsal horn neurons were made in vivo to study alterations in their responsiveness caused by 2 injections of NGF into the multifidus muscle at an interval of 5 days. ⋯ Important findings were that the proportion of neurons having multiple receptive fields (RFs) in various tissues was significantly higher after 2 NGF injections, and new RFs appeared on the distal hind limb. The new RFs were located not in the skin but in deep tissues (muscles, thoracolumbar fascia). If similar changes occur in patients, the data might explain the diffuse nature and spread of myofascial low back pain.
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Randomized Controlled Trial
Cortico-subcortical activation patterns for itch and pain imagery.
The imagery of itch and pain evokes emotional responses and covert motor responses (scratching to itch and withdrawal to pain). This suggests some similarity in cerebral mechanisms. However, itch is more socially contagious than pain, as evidenced by the fact that scratching behaviors can be easily initiated by watching itch-inducing situations, whereas withdrawal is less easily initiated by watching painful situations. ⋯ Connectivity with the aIC was stronger in the primary motor and premotor cortices during pain imagery and stronger in the globus pallidus during itch imagery. These findings indicate that brain regions associated with imagery of itch are the same as those involved in imagery of pain, but their functional networks differ. These differences in brain networks may explain why motor responses to itch are more socially contagious than those related to pain.
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We have modeled the transition from acute to chronic pain in the rat. In this model (termed hyperalgesic priming) a chronic state develops after a prior inflammatory process or exposure to an inflammatory mediator, in which response to subsequent exposure to prostaglandin E2 (PGE2) is characterized by a protein kinase Cε-dependent marked prolongation of mechanical hyperalgesia. To assess the effect of priming on the function of the nociceptor, we have performed in vitro patch clamp and in vivo single-fiber electrophysiology studies using tumor necrosis factor α to induce priming. ⋯ However, 60 minutes after PGE2 administration, the response to mechanical stimulation was further increased in primed but not in control nociceptors. Thus, at the level of the primary afferent nociceptor, it is possible to demonstrate both altered function at baseline and prolonged PGE2-induced sensitization. Intrathecal antisense (AS) to Kv7.2, which contributes to RMP in sensory neurons, reversibly prevented the expression of priming in both behavioral and single-fiber electrophysiology experiments, implicating these channels in the expression of hyperalgesic priming.