Signal transduction in neuropathic pain, with special emphasis on the analgesic role of opioids - Part II: Moving basic science towards a new pharmacotherapy

In the first part of this three-part article I explored the notion that pharmacological intervention, aimed at eliminating abnormal sensations such as hyperalgesia or paraesthesia arising as a direct result of nerve injury, activates adaptive responses that ensure adequacy of neurotransmission, regardless of whether such transmission ultimately evokes normal or abnormal sensations. Thus, by their nature, such adaptive responses will act to oppose and surmount any drug-induced intervention designed to diminish pain through attenuation of signal conduction. A corollary of this hypothesis is that even the most sophisticated novel pharmacological entities, when used to block the pain signal, represent substrates for evoking a repertoire of failsafe mechanisms that have evolved throughout a history of challenge and response. In Part II, I explore in greater depth how activation of these responses may explain why the treatment of neuropathic pains, particularly with opioids, can be so frustrating.