Pain
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After peripheral nerve injury, nociceptive afferents acquire an abnormal excitability to adrenergic agents, possibly due to an enhanced expression of α1-adrenoceptors (α1-ARs) on these nerve fibres. To investigate this in the present study, changes in α1-AR expression on nerve fibres in the skin and sciatic nerve trunk were assessed using immunohistochemistry in an animal model of neuropathic pain involving partial ligation of the sciatic nerve. In addition, α1-AR expression on nerve fibres was examined in painful and unaffected skin of patients who developed complex regional pain syndrome (CRPS) after a peripheral nerve injury (CRPS type II). ⋯ In each patient examined, α1-AR expression was greater on nerve fibres in skin affected by CRPS than in unaffected skin from the same patient or from pain-free controls. Together, these findings provide compelling evidence for an upregulation of α1-ARs on cutaneous nociceptive afferents after peripheral nerve injury. Activation of these receptors by circulating or locally secreted catecholamines might contribute to chronic pain in CRPS type II.
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Large conductance calcium-activated potassium (BKCa) channels are important regulators of neuronal excitability. Although there is electrophysiological evidence for BKCa channel expression in sensory neurons, their in vivo functions in pain processing have not been fully defined. Using a specific antibody, we demonstrate here that BKCa channels are expressed in subpopulations of peptidergic and nonpeptidergic nociceptors. ⋯ However, their behavior in models of neuropathic or acute nociceptive pain was normal. Moreover, systemic administration of the BKCa channel opener, NS1619, inhibited persistent inflammatory pain. Our investigations provide in vivo evidence that BKCa channels expressed in sensory neurons exert inhibitory control on sensory input in inflammatory pain states.
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Randomized Controlled Trial
Repetitive Transcranial Magnetic Stimulation Induced Analgesia Depends on N-Methyl-D-Aspartate Glutamate Receptors.
We investigated the role of glutamate N-methyl-d-aspartate (NMDA) receptors in the analgesic effects induced by repetitive transcranial magnetic stimulation (rTMS). In a randomized, double-blind, crossover study, we compared the effects of ketamine and placebo on the analgesic effects of motor cortex (M1) or dorsolateral prefrontal cortex/premotor cortex (DLPFC/PMC) stimulation. Three groups of 12 healthy volunteers underwent active rTMS (10Hz, 80% resting motor threshold, 1,500 pulses per session) of the right M1, active stimulation of the right DLPFC/PMC, or sham stimulation during 2 experimental sessions 2 weeks apart. ⋯ Ketamine injection significantly decreased the analgesic effects of both M1 and DLPFC/PMC stimulation. The decrease in the analgesic effect of rTMS was not associated with changes in cortical excitability parameters, which were not influenced by rTMS following the administration of either saline or ketamine. Thus, rTMS-induced analgesia depends on glutamate NMDA receptors and may involve long-term potentiation-like mechanisms.