oxytocin and Facial-Pain

Approximately 1.7 million Americans sustain a traumatic brain injury (TBI) each year and chronic pain is a common complication.. We studied the effects of intranasally administered oxytocin as a potential treatment for chronic pain in an animal model of mild TBI.. The lateral fluid percussion model of mild TBI was chosen for this purpose and after exposure to mild TBI the rats (n = 12) developed hind paw and facial allodynia compared to sham animals (n = 6). Oxytocin or a vehicle was afterwards administered intranasally and reactive pain was assessed by hind paw and facial von Frey testing. Some animals received the oxytocin receptor antagonist, atosiban, in addition to oxytocin/vehicle treatment (n = 12). The effect of oxytocin on ongoing and spontaneous pain was examined through conditioned place preference testing. To determine whether the effects of intranasal oxytocin could be attributed to delivery via the peripheral blood stream, some TBI animals received an intravenous injection of the same oxytocin dose that was given intranasally. ELISA immunoassays were carried out (n = 6) to measure concentrations of oxytocin in the trigeminal ganglia, pons, spinal cord, and olfactory bulb after intranasal administration and evaluate the most likely route of entry.. These studies confirmed that the fluid percussion model can be used to study post-TBI facial allodynia. Oxytocin attenuated both reactive and spontaneous, ongoing non-reactive pain following mild TBI for at least 3-4 hours after intranasal administration by binding to OT or VA1-receptors most likely by a peri-trigeminal nerve mediated uptake.. Intranasal oxytocin attenuates measures of reactive and non-reactive pain in a model of mild TBI and may represent a novel treatment for chronic pain in TBI patients.

Topics: Administration, Intranasal; Administration, Intravenous; Animals; Behavior, Animal; Brain Concussion; Chronic Pain; Disease Models, Animal; Facial Pain; Hormone Antagonists; Hyperalgesia; Male; Oxytocin; Random Allocation; Rats; Rats, Sprague-Dawley; Receptors, Oxytocin; Vasotocin

Oxytocin (OXT) is a neuropeptide hormone synthesized and secreted by hypothalamic neurons and has been reported to play a significant role in pain modulation. However, the mechanisms underlying OXT's antinociceptive effect on neuropathic pain are not fully understood. In this study, we examined the peripheral effect of OXT on mechanical hypersensitivity induced by partial ligation of the infraorbital nerve (PNL) in rats. Mechanical hypersensitivity in the whisker pad skin after PNL was attenuated by the direct administration of OXT into the trigeminal ganglion (TG). The proportion of vasopressin-1A receptor (V1A-R)-immunoreactive, but not OXT-receptor-immunoreactive, neurons significantly increased among TG neurons innervating the whisker pad skin after PNL. In a patch-clamp recording from TG neurons isolated from PNL rats, the resting membrane potential of OXT-treated neurons was significantly decreased, and the current thresholds of OXT-treated neurons for spike generation (rheobases) were significantly greater than those of vehicle-treated neurons. In addition, OXT increased voltage-gated K channel currents in PNL animals. Furthermore, intra-TG administration of a selective V1A-R antagonist reversed the OXT-induced alleviation of mechanical hypersensitivity, and coapplication of the antagonist opposed OXT's effects on the resting membrane potential, rheobase, and K current. These findings suggest that OXT is effective at suppressing TG neuronal hyperexcitability after nerve injury, likely by modulation of voltage-gated K channels through V1A-R. This signaling mechanism represents a potential therapeutic target for the treatment of orofacial neuropathic pain.

Topics: Animals; Cells, Cultured; Disease Models, Animal; Facial Pain; Hormone Antagonists; Hyperalgesia; Indoles; Male; Membrane Potentials; Neurons; Oxytocin; Pain Threshold; Pyrrolidines; Rats; Rats, Sprague-Dawley; Receptors, Oxytocin; Receptors, Vasopressin; Trigeminal Ganglion; Vibrissae