Pain behavior and response properties of spinal dorsal horn neurons following experimental diabetic neuropathy in the rat: Modulation by nitecapone, a COMT inhibitor with antioxidant properties
A. Pertovaara et al., Pain behavior and response properties of spinal dorsal horn neurons following experimental diabetic neuropathy in the rat: Modulation by nitecapone, a COMT inhibitor with antioxidant properties, EXP NEUROL, 167(2), 2001, pp. 425-434
We attempted to characterize a spinal neuronal correlate of painful neuropa
thy induced by diabetes mellitus (DM), Pain behavior and response propertie
s of spinal dorsal horn neurons were determined in rats with a streptozocin
-induced DM, A catechol-O-methyltransferase inhibitor with potent antioxida
nt properties, nitecapone, was used in an attempt to attenuate neuropathic
symptoms. Behaviorally DM induced mechanical hypersensitivity that was mark
edly attenuated by oral treatment with nitecapone, The antihyperalgesic eff
ect of nitecapone was not reversed by naloxone, an opioid antagonist, or at
ipamezole, an alpha -2-adrenoceptor antagonist. Electrophysiological record
ings performed in pentobarbitone-anesthetized animals revealed that the mos
t distinct abnormality in response properties of spinal dorsal horn wide-dy
namic range (WDR) neurons was the increase in their spontaneous activity ob
served in untreated but not in nitecapone-treated DM rats. Conditioning ele
ctrical stimulation and a lidocaine block of the rostroventromedial medulla
(RVM) had a similar modulatory effect on evoked responses of spinal dorsal
horn WDR neurons in all experimental groups. The response properties of sp
inal dorsal horn nociceptive-specific or low-threshold mechanoreceptive neu
rons were not markedly different between the experimental groups, The resul
ts indicate that increased spontaneous activity in spinal dorsal horn WDR n
eurons may be causally related to behaviorally observed mechanical hypersen
sitivity in DM. Attenuation of the increased spontaneous activity in WDR ne
urons may explain the antihyperalgesic effect by nitecapone, due to naloxon
e- and alpha -2-adrenoceptor-insensitive mechanisms. DM or nitecapone treat
ment did not produce significant changes in phasic or tonic descending pain
regulation originating in the RVM. (C) 2001 Academic Press.