Antinociception vs motor effects of intrathecal vasopressin as measured by four pain tests.

The effects of intrathecal (i.t.) vasopressin (VP) on nociception were quantitatively tested in rats using 4 pain tests: tail flick, tail shock vocalization, hot plate, and formalin. In addition, motor effects of VP were examined qualitatively. I.t. VP produced a prolonged antinociception lasting at least 40 min on the tail flick (2.5 and 25 ng) and formalin (25 ng) tests, and a brief antinociception lasting less than 20 min on the tail shock (25 ng) and hot plate (25 ng) tests. Those rats not responding to the pain tests showed no signs of perceiving the pain stimulus, such as orientation to the stimulus or vocalization. In addition, i.t. VP produced scratching bouts (2.5 and 25 ng) and suppressed hindbody motor function (25 ng). The motor inhibitory effects of VP, although severe in some rats, were brief, lasting less than 15 min. In conclusion, i.t. VP produces antinociception in addition to its motor effects, and these properties appear to be due to separate mechanisms.

Role of spinal cord neuropeptides in pain sensitivity and analgesia: thyrotropin releasing hormone and vasopressin.

The existence of a wide variety of neuropeptides within the spinal cord dorsal horn raises the question of their possible roles in sensory processing. The present series of behavioral experiments examined the effects of intrathecal (IT) administration of two such neuropeptides, thyrotropin-releasing hormone (TRH) and vasopressin (VAS), on pain sensitivity and antinociception. TRH exerted no marked effect on basal pain sensitivity over the dose range examined (0.25 ng-2.5 micrograms). However, a U-shaped dose-response effect on morphine antinociception (3 micrograms, IT) was observed, wherein potent attenuation, moderate attenuation, or enhancement of morphine-induced antinociception was observed following the various doses tested. In contrast, VAS produced non-opiate antinociception at the highest doses tested (25 ng and 250 ng) and none of the VAS doses (0.25 ng-250 ng) appeared to interact with IT morphine (3 micrograms) antinociception. Lastly, IT TRH was not observed to interact with IT VAS antinociception. These data provide evidence that these neuropeptides exert strikingly different effects on pain sensitivity and opiate antinociception, and provide initial evidence that TRH may be included in the growing list of neuropeptides that can act like endogenous opiate antagonists within the central nervous system.

Inhibition of spinal dorsal horn neuronal responses to noxious skin heating by lateral hypothalamic stimulation in the cat.

The responses of single lumbar dorsal horn units to noxious radiant heating (50 degrees C, 10 s) of glabrous foot pad skin were recorded in cats anesthetized with sodium pentobarbital and 70% N2O. The heat-evoked responses of each of 38 units were markedly reduced during electrical stimulation (100-ms trains at 100 Hz, 3/s, 25-300 microA) in the lateral hypothalamic area (LH). LH sites at which stimulation inhibited dorsal horn unit heat-evoked responses were mapped by systematically varying the position of the stimulating electrode. Inhibition was generated at posterior through anterior hypothalamic levels in a region extending laterally from the periventricular gray (PVG) to the cerebral peduncles on both sides and ventrally to the base of the brain. The magnitude of inhibition increased with graded increases in LH stimulation intensity. Respective mean current intensities at threshold for generating inhibition were 27.6 +/- 17.4 (SD) microA for contralateral and 30.1 +/- 23.7 microA for ipsilateral LH stimulation. Dorsal horn unit responses to a series of graded noxious heat stimuli generally increased linearly from threshold (38-45 degrees C) to 52 degrees C. The slopes of such linear temperature-response functions were reduced, with no significant change in threshold, when the temperature series was repeated during concomitant ipsilateral LH stimulation. Contralateral LH stimulation produced similar slope reductions but additionally produced a significant mean threshold increase of 1.7 degrees C. The inhibitory effect of LH stimulation was significantly reduced in nine units from a mean of 28 +/- 18% of control to a mean of 59 +/- 18% following systemic administration of the serotonin (5-hydroxytryptamine, 5-HT) antagonist, methysergide (0.3-1 mg/kg). Possible functional relationships of LH with brain stem inhibitory systems and its role in analgesic mechanisms are discussed.