We are studying an endogenous, oxytocinergic analgesia system to obtain more information about normal and pathological pain processes. In the recent years, this oxytocinergic system has been shown to be involved in normal and pathological pain suppression. The paraventricular nucleus (PVN) of the hypothalamus is an important source of brain oxytocin (OT). A descending pathway reaching the dorsal horn in the spinal cord was postulated to mediate analgesic effects at the spinal cord level. However, the oxytocin concentration during pain conditions and during PVN electrical stimulation needs to be determined. We designed experiments to measure the OT concentration in cerebrospinal fluid (CSF), plasma, and OT protein in lumbar spinal cord tissue in control and neuropathic rats. Sciatic loose ligature was used as the experimental method to produce neuropathic pain. The main findings were (1) Chronic pain experiments in animals showed that the stimulation of the anterior part of the PVN increased OT concentration and produced analgesia states, as measured by von Frey, cold, and heat plantar tests. (2) Differential effects were produced by electrical stimulation of the anterior or posterior regions of the PVN; electrical stimulation of the anterior part of the PVN enhanced the OT concentration in CSF and plasma, and it also increased OT protein concentrations in the spinal cord tissue; in contrast, the stimulation of the posterior part of the PVN only increased OT concentrations in CSF. These results suggest the participation of an endogenous analgesia system mediated by OT.

Oxytocin (OT) has emerged as a mediator of endogenous analgesia in behavioral and electrophysiological experiments. In fact, OT receptors (OTRs) in the spinal dorsal horn participate in a selective inhibition of the neuronal activity mediated by Aδ and C fibers but not Aβ fibers. This study shows that OTRs are expressed in the terminal nerve endings and are able to inhibit nociceptive neuronal firing. Indeed, local peripheral OT blocked the first sensorial activity of Aδ and C fibers recorded in the spinal cord neurons. Furthermore, using the formalin behavioral nociceptive test, we demonstrated that only ipsilateral OTR activation inhibits pain behavior. Our data are reinforced by the fact that the OTR protein is expressed in the sciatic nerve. Consistent with this, immunofluorescence of primary afferent fibers suggest that OTRs could be located in nociceptive-specific terminals of the skin. Taken together, our results suggest that OTRs could be found in nociceptive terminals and that on activation they are able to inhibit nociceptive input.

This brief review of the neurological effects of growth hormone (GH) and gonadotropin-releasing hormone (GnRH) in the brain, particularly in the cerebral cortex, hypothalamus, hippocampus, cerebellum, spinal cord, neural retina, and brain tumors, summarizes recent information about their therapeutic potential as treatments for different neuropathologies and neurodegenerative processes. The effect of GH and GnRH (by independent administration) has been associated with beneficial impacts in patients with brain trauma and spinal cord injuries. Both GH and GnRH have demonstrated potent neurotrophic, neuroprotective, and neuroregenerative action. Positive behavioral and cognitive effects are also associated with GH and GnRH administration. Increasing evidence suggests the possibility of a multifactorial therapy that includes both GH and GnRH.