Sensitization of high mechanothreshold superficial dorsal horn and flexor motor neurones following chemosensitive primary afferent activation.
Nociceptive primary afferents have the capacity to induce a state of increased excitability or central sensitization in dorsal horn neurones. This contributes to the mechanical hypersensitivity (allodynia) which occurs after peripheral tissue injury where low-mechanothreshold primary afferent activation begins to elicit pain. The relative susceptibility of dorsal horn cells with an apparent exclusive nociceptive input (nociceptive-specific (NS) or high-threshold (HT) cells) and those with a convergent input from low- and high-threshold mechanoreceptors (wide-dynamic-range (WDR) or multireceptive neurones) to sensitivity changes has been disputed. We have examined whether high-mechanothreshold neurones in the superficial dorsal and the ventral horn can modify their sensitivity following cutaneous application of the chemical irritant mustard oil. This produced both a prolonged reduction in the mechanical threshold of the cutaneous flexion withdrawal reflex, recorded from semitendinosus alpha-motor neurones, and an increase in the activity evoked in these neurones by low-intensity touch stimuli to the glabrous skin. Eight NS or HT only cells, defined in terms of their cutaneous mechanoreceptive field properties, were recorded in the superficial dorsal horn before and after cutaneous application of mustard oil. Mustard oil was applied outside of the mechanical receptive field of the cells and produced a transient increase in action potential discharge in 4 cells but increased the mechanoreceptive field size in all cells for 30-60 min. Mechanical thresholds declined in 6 cells to levels associated with low-threshold (LT) and WDR cells, and this was accompanied by recruitment of a novel brush/touch response in 5 cells. The responses evoked by graded electrical stimulation of the sural nerve were tested in 5 cells. Only 1 cell failed to show any change after mustard oil. In 3 cells, an increase in the response to A-fibre afferents occurred, a novel A-fibre response was recruited in 2 cells and the C-fibre response increased in 2 cells. Cells in the superficial dorsal horn of the rat spinal cord that are normally NS can begin, therefore, to respond to LT primary afferent mechanoreceptors after an increase in central excitability produced by activation of peripheral chemoreceptors. Sensitization of these, as well as of WDR cells, may contribute to the generation of post-injury mechanical pain and reflex hypersensitivity.
Woolf
Clifford J
CJ
Department of Anatomy and Developmental Biology, University College London, London WC1E 6BT UK.
Shortland
Peter
P
Sivilotti
Lucia G
LG
D000818:Animals; D002628:Chemoreceptor Cells / Q000187:drug effects / Q000502:physiology*; D003655:Decerebrate State / Q000503:physiopathology; D004558:Electric Stimulation; D008465:Mechanoreceptors / Q000187:drug effects / Q000502:physiology*; D009046:Motor Neurons / Q000187:drug effects / Q000502:physiology*; D009149:Mustard Plant; D009412:Nerve Fibers / Q000187:drug effects / Q000502:physiology; D009413:Nerve Fibers, Myelinated / Q000187:drug effects / Q000502:physiology; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology*; D009619:Nociceptors / Q000187:drug effects / Q000502:physiology; D010812:Physical Stimulation; D010936:Plant Extracts / Q000494:pharmacology; D010938:Plant Oils; D010946:Plants, Medicinal; D051381:Rats; D012018:Reflex / Q000502:physiology; D012684:Sensory Thresholds / Q000187:drug effects / Q000502:physiology*; D013116:Spinal Cord / Q000166:cytology / Q000502:physiology*; D013268:Stimulation, Chemical; D013497:Sural Nerve / Q000502:physiology
D010936:Plant Extracts; D010938:Plant Oils; C027793:mustard oil