Massage-like stroking induces acute antinociceptive effects that can be reversed by an oxytocin antagonist, indicating activation of oxytocin on endogenous pain controlling systems. We now demonstrate an increase in hindpaw withdrawal latencies (HWLs), in response to thermal and mechanical stimuli, which was present after six treatments of massage-like stroking every other day and which continued to increase through the remaining seven treatments. Repeated massage-like stroking also resulted in increased oxytocin-like immunoreactivity (oxytocin-LI) levels in plasma and periaquaductal grey matter (PAG). Furthermore, increases in HWLs were also present after injections of oxytocin into the PAG (0.1, 0.5 and 1.0 nmol). Intra-PAG oxytocin injection of 1 nmol followed by 1 or 20 nmol of naloxone attenuated the increments in HWL. Also, there was a dose-dependent attenuation of the oxytocin-induced antinociceptive effects following intra-PAG injection of the mu-opioid antagonist beta-funaltrexamine (beta-FNA) and the kappa-opioid antagonist nor-binaltorphimine (nor-BNI) but not the delta-antagonist naltrindole. The long-term antinociceptive effects of massage-like stroking may be attributed, at least partly, to the oxytocinergic system and its interaction with the opioid system, especially the mu- and the kappa-receptors in the PAG.

It is well known that the sufficient descent condition is very important to the global convergence of the nonlinear conjugate gradient method. In this paper, some modified conjugate gradient methods which possess this property are presented. The global convergence of these proposed methods with the weak Wolfe-Powell (WWP) line search rule is established for nonconvex function under suitable conditions. Numerical results are reported.

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