Non-opioid actions of lamotrigine within the rat dorsal horn after inflammation and neuropathic nerve damage

Some opioid-resistant pain conditions can be alleviated by voltage-dependen t Na+ channel blockers such as lamotrigine. The mu -opioid-receptor agonist morphine can modulate cation entry into cells to affect overall cellular e xcitability, an effect which can in turn be endogenously antagonised by the neuropeptide cholecystokinin (CCK). However. lamotrigine: may also modulat e cellular excitability by non-specifically blocking voltage-dependent ion channels. We have looked for interactions of lamotrigine with the opioid/CC K pathway within the spinal dorsal horn, to rule out the possibility that l amotrigine may attenuate nociceptive responses via actions on this: pathway . Both lamotrigine and the mu -opioid agonist DAMGO inhibited mustard oil-e voked cell firing by approximately 50% compared with control levels. Go-app lication of CCK8S reversed DAMGO-. but not lamotrigine-induced inhibition o f cell firing and this reversal was prevented with the selective CCK, recep tor antagonist PD 135158. Although lamotrigine inhibited both brush- and co ld-evoked cell firing in neuropathic animals, lamotrigine inhibition of mus tard oil-evoked cell firing in the same animals was not significantly great er than that observed in controls. These results suggest that the antinocic eptive properties of lamotrigine within the spinal dorsal horn are unlikely to be mediated via interactions with the opioid/CCK pathway. (C) 2001 Else vier Science Ireland Ltd and the Japan Neuroscience Society. All rights res erved.