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American Society for Action on Pain

UI - 000108

AU - Dickenson AH

AU - Sullivan AF

TI - Subcutaneous formalin-induced activity of dorsal horn neurones in the rat: differential response

to an intrathecal opiate administered pre or post formalin

AB - Many studies of pain and nociception use short-lasting acute stimuli which may have limited relevance

to prolonged or chronic pain states. Using extracellular single-unit recording in the dorsal horn of the rat

lumbar spinal cord the present study examines the response of neurones to a long-lasting nociceptive

stimulus, i.e., 50 microliter 5% formalin injected into the corresponding receptive field in the ipsilateral hind

paw, and modulation of this response by an opioid. Formalin produced a distinct biphasic excitatory

response in all convergent neurones tested; an immediate acute or phasic peak of neuronal firing (mean

maximum 22 spikes/sec) 0-10 min post injection, and a second more prolonged tonic excitatory response

(mean maximum 12 spikes/sec) over a period 20-65 min after formalin. Cells only activated by innocuous

stimuli were not excited by formalin indicating the involvement of C fibre afferents in the excitatory response

of convergent neurones to formalin. Both the biphasic nature and the time course of the neuronal response

are similar to those observed in behavioural studies. Intrathecal DAGO (Tyr-D-AlaGlyMePheGly-ol), a

potent and selective mu opioid receptor agonist, applied 20 min prior to formalin completely inhibited both

peaks of excitation. Co-administration of intrathecal naloxone with the agonist restored the biphasic

response. By contrast, when the administration of naloxone was delayed to 2 min post formalin so that

inhibition of the first peak by DAGO pretreatment occurred, there was no subsequent second peak of

activity although antagonism of the opioid would have occurred. When DAGO was applied 2 min post

formalin so the initial acute response occurred, the inhibitory effect of the agonist on the second peak was

far less. Thus the relative ability of DAGO to modulate the biphasic excitatory response of cells to formalin

depends on whether the agonist is administered prior to or after the formalin and the appearance of the

second peak may depend on the presence of the first. These results are discussed in light of the role of these

neurones in nociception, opioid effects and changes in neural systems following peripheral stimuli

SO - Pain 1987;30:349-360