Footshock-induced analgesia: Neurochemical correlates and pharmacological profile

The administration of electric shock to the feet of rats can produce either opioid, naloxone-sensitive analgesia or non-opioid, naloxone-insensitive analgesia. In our hands opioid analgesia could be elicited in young Sabra rats (75 days of age) by all analgesia induction methods while older rats of the same strain and rats of the Charles River-derived strain (CR) showed only naloxone-resistant analgesia. We therefore compared the effects of 2 different footshock parameters, 3 min continuous shock (3 mA) and 30 min intermittent shock (30 min, 1 s on 5 s off) on the responsiveness to noxious stimuli and on brain enkephalins and humoral (H-) endorphin content in these strains of rats. As previously reported, only young Sabra rats showed opioid analgesia whereas all other animals displayed naloxone-resistant effects. In contrast, no differential effects on brain opioids could be seen in these species. Thus, 30 min of shock produced a significant increase in brain enkephalins and a noticeable albeit non-significant increase in brain H-endorphin. A slight non-significant increase was seen following brief footshock. To asses the nature of non-opioid analgesia further we examined the effects of both reserpine and a series of antagonists on the analgesia produced by 3 and 30 min of either brief or prolonged shock. Pretreatment with reserpine caused a significant attenuation of non-opioid analgesia with both shock parameters while none of the antagonists administered (methysergide, phentolamine, phenoxybenzamine, yohimbine, theophyline, diphenhydramine and scopolamine) were effective. In view of the increase in brain opioids following prolonged footshock and the ability of reserpine to attenuate non-opioid analgesia we tested whether reserpine pretreatment could 'unveil' opioid analgesia in naloxone-resistant CR and adult Sabra rats. Indeed, a naloxone-reversible analgesic component was evident in reserpine-pretreatment adult Sabras but not in animals of the CR strain. We therefore propose that analgesia induction by non-pharmacological manipulations is a function of the release of naloxone-sensitive enkephalins and substances which are relatively insensitive to naloxone, such as H-endorphin, and that the relative contribution is determined by both genetic and ontogenetic factors. The ability of reserpine to reverse both opioid and non-opioid analgesia indicates the involvement of monoamines in these forms of analgesia, the nature of which cannot yet be determined.