Introduction
The effect of diabetes mellitus (DM) on pain transmission and descending pain regulation within the central nervous system has been only little studied. In the present study we attempted to characaterize the effects of DM on response properties and descending modulation of spinal dorsal horn neurons in rats with a behaviorally verified neuropathy. Nitecapone, a catechol-O-methyltransferase inhibitor with potent antioxidant properties was used in an attempt to attenuate neuropathic symptoms.
Methods
DM was induced by streptozotocin. Neuropathy was assessed behaviorally by determining hindlimb withdrawal thresholds to mechanical stimulation and tail-flick response to heat stimulation. Electrophysiological microelectrode recordings were made from the spinal dorsal horn neurons under pentobarbitone anesthesia. One group of diabetic animals was treated per orally with nitecapone. A group of healthy rats served as a control.
Results
Behaviorally DM induced a mechanical hypersensitivity that was attenuated by nitecapone. The effect of nitecapone was not reversed by an alpha-2-adrenoceptor or opioid receptor antagonist. Tail flick latencies were prolonged in DM and this prolongation was associated with a skin temperature decrease. Electrophysiological recordings revealed that the most prominent change in response properties of wide-dynamic range (WDR) spinal dorsal horn neurons was an increase in their spontaneous activity that was observed in untreated but not in nitecapone-treated diabetic animals. Conditioning electrical stimulation or lidocaine block of the rostroventromedial medulla (RVM) had a similar modulatory effect on evoked responses to spinal dorsal horn WDR neurons in all experimental groups. The response properties of nociceptive-specific or low-threshold mechanoreceptive spinal dorsal horn neurons were not markedly different between the experimental groups. Blood glucose levels were equally increased and body weights equally decreased in untreated and nitecapone-treated diabetic animals. Motor performance in the Rotarod test was equal in all experimental groups whereas spontaneous locomotor activity (open-field test) was equally decreased in untreated and nitecapone-treated diabetic animals.
Conclusions
The results suggest that increased spontaneous activity in spinal dorsal horn WDR neurons may be causally related to behaviorally observed mechanical hypersensitivity in diabetic rats. The increased tail-flick latencies induced by radiant heat may be explained by a skin temperature-related artifact. The attenuation of neuropathic symptoms by nitecapone may be explained by attenuation of spontaneous activity in WDR neurons, due to opioid- and alpha-2-adrenoceptor insensitive mechanisms. DM or nitecapone do not produce marked changes in phasic or tonic descending pain regulation originating in the RVM.
References