Elsevier

Experimental Neurology

Volume 149, Issue 1, January 1998, Pages 193-202
Experimental Neurology

Regular Article
A Neuronal Correlate of Secondary Hyperalgesia in the Rat Spinal Dorsal Horn Is Submodality Selective and Facilitated by Supraspinal Influence

https://doi.org/10.1006/exnr.1997.6688Get rights and content

Abstract

Tissue injury produces hyperalgesia not only in the injured area (primary hyperalgesia) but also outside of it (secondary hyperalgesia). In the present investigation, the submodality selectivity and the contribution of supraspinal influence to a neural correlate of the secondary hyperalgesia induced by neurogenic inflammation was studied in the presumed pain relay neurons of the rat spinal dorsal horn. Mechanically and thermally evoked responses to wide-dynamic range (WDR) neurons of the spinal dorsal horn were recorded under sodium pentobarbital anesthesia in rats. Neurogenic inflammation was induced by application of mustard oil outside of the receptive fields of WDR neurons. To study the contribution of supraspinal influence to mustard oil-induced changes in neuronal responses, the spinal cord was transected at a midthoracic level or lidocaine was microinjected into the rostroventromedial medulla (RVM). Furthermore, the antidromically evoked compound volley in the sural nerve was determined to reveal excitability changes in the central terminals of primary afferent A-fibers induced by mustard oil. The results indicate that mustard oil adjacent to the receptive fields of spinal WDR neurons significantly enhanced their responses to mechanical but not to noxious heat stimuli, without a significant influence on their spontaneous activity. Both high- and low-threshold mechanoreceptive input to WDR neurons was equally facilitated, whereas mechanoreceptive input to spinal dorsal horn neurons mediating innocuous messages (low-threshold mechanoreceptive neurons) was not changed. Mustard oil in a remote site (forepaw) did not produce any hyperexcitability to responses evoked by hindpaw stimulation. Spinal transection or lidocaine block of the RVM significantly attenuated the mustard oil-induced mechanical hyperexcitability in spinal dorsal horn neurons. Mustard oil had no significant effect on a compound A-volley in the sural nerve induced by intraspinal stimulation of sural nerve terminals at a submaximal intensity. The selective mechanical hyperexcitability in spinal WDR neurons, without a change in their spontaneous activity, can be explained by a heterosynaptic facilitatory action on presynaptic terminals mediating mechanical signals to these nociceptive spinal neurons. These findings indicate that brain stem–spinal pathways, involving the RVM, do not only suppress nociception but under some pathophysiological conditions concurrent facilitatory influence may predominate and lead to enhancement of mechanical hyperexcitability. The descending facilitatory feedback loop to nociceptive spinal neurons may help to protect the wounded tissue and thus promote healing.

References (57)

  • J.F. Herrero et al.

    Supraspinal influence on the facilitation of rat nociceptive reflexes induced by carrageenan monoarthritis

    Neurosci. Lett.

    (1996)
  • C.J. Hodge et al.

    Changes in the effects of stimulation of locus coeruleus and nucleus raphe magnus following dorsal rhizotomy

    Brain Res.

    (1983)
  • M. Koltzenburg et al.

    Dynamic and static components of mechanical hyperalgesia in human hairy skin

    Pain

    (1992)
  • D. Lebars et al.

    Diffuse noxious inhibitory controls (DNIC). I. Effects on dorsal horn convergent neurones in the rat

    Pain

    (1979)
  • H. Mansikka et al.

    Supraspinal influence on hindlimb withdrawal thresholds and mustard oil-induced secondary allodynia in rats

    Brain Res. Bull.

    (1997)
  • H. Mansikka et al.

    Different roles of α2

    Eur. J. Pharmacol.

    (1996)
  • J.H. Martin

    Autoradiographic estimation of the extent of reversible inactivation produced by microinjection of lidocaine and muscimol in the rat

    Neurosci. Lett.

    (1991)
  • A. Pertovaara et al.

    Lidocaine in the rostroventromedial medulla and the periaqueductal gray attenuates allodynia in neuropathic rats

    Neurosci. Lett.

    (1996)
  • A. Pertovaara et al.

    Chronic spinal nerve ligation induces changes in response characteristics of nociceptive spinal dorsal horn neurons and in their descending regulation originating in the periaqueductal gray in the rat

    Exp. Neurol.

    (1997)
  • P.W. Reeh et al.

    Does neurogenic inflammation alter the sensitivity of unmyelinated nociceptors in the rat

    Brain Res.

    (1986)
  • H.-G. Schaible et al.

    Afferent and spinal mechanisms of joint pain

    Pain

    (1993)
  • D.A. Simone et al.

    Sensitization of cat dorsal horn neurons to innocuous mechanical stimulation after intradermal injection of capsaicin

    Brain Res.

    (1989)
  • L.S. Sorkin et al.

    Amino acids and serotonin are released into the lumbar spinal cord of the anesthetized cat following intradermal capsaicin injection

    Brain Res.

    (1993)
  • R.-D. Treede et al.

    Peripheral and central mechanisms of cutaneous hyperalgesia

    Prog. Neurobiol.

    (1992)
  • M.O. Urban et al.

    Participation of central descending nociceptive facilitatory systems in secondary hyperalgesia

    Brain Res.

    (1996)
  • A.L. Vaccarino et al.

    Temporal processing of formalin pain: Differential role of the cingulum bundle, fornix pathway and medial bulboreticular formation

    Pain

    (1992)
  • E.P. Wiertelak et al.

    Subcutaneous formalin produces centrifugal hyperalgesia at a noninjected site via the NMDA-nitric oxide cascade

    Brain Res.

    (1994)
  • C.J. Woolf

    Long term alterations in the excitability of the flexion reflex produced by peripheral tissue injury in the chronic decerebrate rat

    Pain

    (1984)
  • Cited by (97)

    View all citing articles on Scopus
    View full text