DIFFERENTIAL-EFFECTS OF INTRATHECALLY ADMINISTERED DELTA-OPIOID AND MU-OPIOID RECEPTOR AGONISTS ON FORMALIN-EVOKED NOCICEPTION AND ON THE EXPRESSION OF FOS-LIKE IMMUNOREACTIVITY IN THE SPINAL-CORD OF THE RAT

This study examined the effects of intrathecally (i.t.) administered m u and delta opioid receptor agonists on the flinching behavior and the expression of Fos-like immunoreactivity (Fos-LI) in the spinal cord e licited by s.c. injection of 5% formalin in one hindpaw of the rat. In trathecal pretreatment with either the delta-1 opioid receptor agonist [D-Pen(2,5)]enkephalin (DPDPE) or the delta-2 opioid receptor agonist [D-Ala(2),Glu(4)]deltorphin (DELT) produced a dose-dependent inhibiti on of flinching behavior in phase 1 and phase 2 that was antagonized b y coadministration of the delta-1 opioid receptor antagonist 7-benzyli dinenaltrexone or the delta-2 opioid receptor antagonist Naltriben, re spectively. Although i.t. pretreatment with 60 mu g of DPDPE produced a small decrease in the numbers of Fos-LI neurons in laminae I, IIi an d IIo, as well as laminae V and VI and laminae VII-X, i.t. pretreatmen t with 30 mu g of DELT did not decrease the number of Fos-LI neurons i n any region of the spinal cord, In contrast, i.t. pretreatment with a n equieffective dose of the mu opioid receptor agonist [D-Ala(2),NMePh e(4),Gly-o\5]enkephalin (DAMGO) not only significantly decreased the n umber of flinches in phase 1 and phase 2, but also nearly completely p revented the expression of Fos-LI in all regions of the spinal cord. T hese effects were antagonized by pretreatment with the mu opioid recep tor antagonist D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Phe-Thr-NH2. The efficacy o f i.t. administered DAMGO suggests that a direct spinal action contrib utes to the inhibition of noxious stimulus-evoked Fos-LI in the spinal cord produced by systemically administered mu opioid receptor agonist s such as morphine. The relative lack of effect of DPDPE or DELT sugge sts that delta opioid receptors do not modulate the early-immediate ge ne c-fos. Alternatively, because delta opioid receptor agonists inhibi t synaptic transmission in the spinal cord by predominantly presynapti c mechanisms and do not hyperpolarize dorsal horn neurons, the excitat ory inputs that persist in the presence of these agonists may be suffi cient to activate the c-fos gene. Taken together, these results provid e new evidence, at the level of a ''third messenger,'' that the antino ciception produced by i.t. administration of delta and mu opioid recep tor agonists is mediated by different mechanisms.