Vaginocervical stimulation attenuates hindpaw shock-induced substance P release into spinal cord superfusates in rats.

The present study was designed to elucidate the mechanism in the spinal cord by which vaginocervical stimulation (VS) attenuates responses to noxious stimulation. This was accomplished by testing the hypothesis that VS reduces noxious stimulation-induced release of substance P at the level of the spinal cord. Noxious foot shock significantly increased the release of substance P (measured using radioimmunoassay) into superfusates of the lumbosacral spinal cord region in urethane-anesthetized rats. VS applied concurrently with foot shock significantly attenuated the release of substance P compared to the foot shock-only condition. In addition, substance P levels were significantly lower after the VS-only condition than after the no stimulation or foot shock-only conditions. These findings indicate that VS may produce analgesia, at least in part, by suppressing the release of substance P within the spinal cord.

Vasoactive intestinal polypeptide (VIP) potentiates the behavioral effect of substance P intrathecal administration.

Intrathecal (IT) injection of 20 micrograms substance P (SP) induced a behavioral syndrome consisting of scratching and biting the flanks (83% and 57%, respectively, of 48 rats), and distress-like vocalization (42% of 26 rats tested) in response to a previously innocuous tactile stimulus with a von Frey fiber (allodynia). These behavioral events following SP were of short latency (1-2 min) and duration (around 10 min). Injection IT of 5 micrograms, but not 1 microgram, of vasoactive intestinal polypeptide (VIP), concurrently with SP, significantly increased the frequency of both scratching and biting bouts over that produced by SP alone. VIP IT alone (1 or 5 micrograms) did not stimulate scratching-biting, but induced allodynia in a significant proportion of rats.

Blockage of substance P-induced scratching behavior in rats by the intrathecal administration of inhibitory amino acid agonists.

Intrathecal administration of 20 micrograms of substance P induced scratching behavior in most tested rats (80%). Scratching appeared in bouts of short latency and variable duration, intensity and frequency (range 1-60, mean number of scratching bouts in one hour test: 8.93 +/- 1.86). Intrathecal administration of glycine (400 micrograms but not 66 micrograms) significantly decreased the effect of substance P on this behavior. Taurine, in dosages equimolar to glycine, abolished the response to substance P at the high dose level (700 micrograms), but did not significantly affect it at the lower level (120 micrograms). The GABAA agonist, muscimol, abolished the effect of substance P at the 3 micrograms dose level, but the 0.5 microgram dose did not produce a significant effect. Baclofen, a GABAB agonist, was highly effective in significantly reducing the action of SP at 0.9 and 0.15 microgram; only two of 8 rats receiving the low dose of baclofen (0.15 microgram) exhibited scratching. The results suggest that the spinal inhibitory amino acids modulate nociceptive impulses generated by the action of substance P in dorsal horn neurons of the spinothalamic tract.

Prevention of the convulsant and hyperalgesic action of strychnine by intrathecal glycine and related amino acids.

Intrathecal administration of 25 micrograms strychnine induced consistent sensory and motor behavioral events in rats. Sensory events included scratching and biting the lower half of the body, spontaneous vocalizations and skin hyperalgesia, evidenced by vocalization and reflex scratching in response to stimulation with a 5.5 g von Frey fiber. This mild stimulus failed to elicit vocalizations in the preinjection condition. Strychnine induced two types of motor seizures: (1) falling over with tail whipping and (2) convulsions. The effect of equimolar doses of glycine (G) and some related amino acids: beta-alanine (A), taurine (T) and betaine (B) on the strychnine syndrome was tested by administering them (intrathecal route) along with strychnine. T and G but not B significantly decreased most of the sensory events triggered by strychnine. All amino acids significantly decreased the incidence and duration of convulsions; T and B abolished them. A decreased vocalizations and skin hyperalgesia but synergized with strychnine to facilitate scratching and self biting. These results are consistent with findings that G, A and T displace strychnine from its binding sites in the CNS.