Central changes in processing of mechanoreceptive input in capsaicin‐induced secondary hyperalgesia in humans.

Abstract

SUMMARY1. Capsaicin, the algesic substance in chilli peppers, was injected intradermally in healthy human subjects. A dose of 100 ,tg given in a volume of 10 ,ul caused intense pain lasting for a few minutes after injection and resulted in a narrow area of hyperalgesia to heat and a wide surrounding area of hyperalgesia to mechanical stimuli (stroking) lasting for 1-2 h.2. Nerve compression experiments with selective block of impulse conduction in myelinated (A) but not in unmyelinated (C) fibres indicated that afferent signals in C fibres contributed to pain from capsaicin injection and to heat hyperalgesia, whereas conduction in afferent A fibres was necessary for the perception of mechanical hyperalgesia.3. Electrical intraneural microstimulation normally eliciting non-painful tactile sensations was accompanied by pain when the sensation was projected to skin areas within the region of mechanical hyperalgesia induced by capsaicin injection.4. The threshold for pain evoked by intraneural microstimulation was reversibly lowered and pain from suprathreshold stimulation was exaggerated during the period of mechanical hyperalgesia, regardless of lidocaine anaesthesia of the cutaneous innervation territory of the stimulated fibres.5. The results indicate that hyperalgesia to stroking on a skin area surrounding a painful intradermal injection of capsaicin is due to reversible changes in the central processing of mechanoreceptive input from myelinated fibres which normally evoke non-painful tactile sensations.

Gene knockdown with intrathecal siRNA of NMDA receptor NR2B subunit reduces formalin-induced nociception in the rat

“…24 This increase in responsiveness to synaptically released glutamate causes pain hypersensitivity far beyond the site and the duration of the C fiber activating stimulus. 25 The formalin test is the most frequently used method for assessing the antihypersensitivity efficacy of NMDA receptor antagonists. 6 The immediate response to intraplantar formalin reflects the activation of primary afferent nociceptors.…”

An update and systematic review on drug therapies for the treatment of refractory chronic cough

“…After peripheral nerve injury, damaged and nondamaged electrophysiological changes particular to central sensitization correlate with the development in human experimental subjects after a noxious conditioning input of allodynia (particularly dynamic tactile or brush-evoked allodynia), the temporal summation of repeated low-intensity stimuli from an innocuous sensation to pain, with ‘after-pain’ on cessation of the stimulus, and widespread secondary hyperalgesia [66]. These changes can be elicited in human volunteers by noxious stimulation of the skin as with topical or intradermal capsaicin or repeated heat stimuli [67], and in the gastrointestinal tract by exposure to low pH solutions [68]. Similar clinical features such as an abnormal laryngeal sensation or throat tickle (laryngeal paresthesia), increased cough sensitivity in response to a known tussigen (hypertussia), and cough triggered in response to non-tussive triggers such as cold air or talking on the phone (allotussia) are seen in refractory CC [65].…”

Preemptive analgesia I: physiological pathways and pharmacological modalities

“…42 Primary hyperalgesia is explained by sensitization of peripheral nociceptors, [44][45][46] while secondary hyperalgesia may be caused by altered CNS processing of mechanoreceptor impulses from peripheral tissues. 45,[47][48][49][50] Clinical pain may be divided into two entities: inflammatory pain, which is the consequence of trauma to peripheral tissues (i.e., surgical incision, dissection, burns, etc); and neuropathic pain, which is the result of direct injury to nervous tissue (i.e., nerve transection). Both types of injury result in long-term changes in the sensitivity of the nervous system, such that the intensity of subsequent stimuli necessary to induce pain is reduced.…”