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G L Wilcox

Publications and source records attributed to G L Wilcox.

70 records · Page 4Linked to original sources
PubMed1984

Synergistic behavioral effects of serotonin and tryptamine injected intrathecally in mice.

The endogenous compounds, serotonin (5-HT) and tryptamine (TA), have been found to alter function in the CNS, supporting the hypothesis that they serve as neurotransmitters. It is reported here that intrathecal injections of either 5-HT or tryptamine elicited similar behavioral syndromes consisting of caudally-directed biting, or licking and scratching. Serotonin was found to be considerably more potent than tryptamine. However, administration of both indoleamines produced synergistic interactions with respect to this behavioral syndrome. Administration of fluoxetine with either 5-HT or tryptamine potentiated the scratching behavior produced by either indoleamine, but failed to enhance the effect of an injection of 5-HT plus tryptamine. Administration of methysergide blocked the effects of both indolamines. The results are discussed in terms of a possible mechanism of the synergism between 5-HT and tryptamine.

Animals↗
PubMed1984

An instrument using a multiple layer Peltier device to change skin temperature rapidly.

A thermal stimulator that uses multiple layer Peltier devices produces rapid heating or cooling of the skin of experimental animals. Rate of change of temperature can be controlled from 1 degree C/sec to 5 degrees/sec (cooling) or to 10 degrees/sec (heating). Rapid thermal transients are not accompanied by thermal overshoot. Maintenance of and return to a preset temperature are within +/- 0.05 degrees.

Animals↗
PubMed1983

Intrathecal serotonin in mice: analgesia and inhibition of a spinal action of substance P.

Serotonin, administered intrathecally in mice, produced dose-related analgesia in the tail flick test and the subcutaneous hypertonic saline assay. Low doses (2.5-5 ng) of serotonin blocked the biting and scratching response elicited by intrathecal substance P. However, higher doses of serotonin itself elicited a behavioral syndrome characterized by scratching of the torso with the hindlimbs. Both the analgesic response and the scratching response due to serotonin were blocked by specific serotonin antagonists and the analgesia is likely mediated by a postsynaptic action on dorsal horn nociceptive neurons.

Analgesia↗
PubMed1983

Pharmacological characterization of substance P-induced nociception in mice: modulation by opioid and noradrenergic agonists at the spinal level.

Mice were tested for antinociceptive activity after intrathecal injection of opioid or noradrenergic agonists by lumbar puncture. Opioid agonists with mu or delta activity and adrenergic agonists with alpha activity demonstrated dose-related, receptor-mediated analgesia in the tail-flick assay, s.c. hypertonic saline assay and the intrathecal substance P behavioral assay. Inhibition of substance P-induced biting and scratching by intrathecally administered antinociceptive agents is likely mediated by post-synaptic receptors. This action of opioids and norepinephrine was antagonized by their respective pharmacological antagonists. Subanalgesic doses of Leu-enkephalin or norepinephrine potentiated the antinociceptive activity of morphine in the substance P assay. Similarly, opioid agonists potentiated the action of norepinephrine. These results suggest that opioid and alpha adrenergic agonists act on separate receptors to produce a synergistic inhibition of the transmission of nociceptive information at the spinal level.

Animals↗
PubMed1982

Intrathecal opioids block a spinal action of substance P in mice: functional importance of both mu- and delta-receptors.

Inhibition of intrathecal substance P-elicited behavior by mu-, delta- and kappa-opioids was compared. In both the substance P behavioral test and the tail flick antinociceptive test, intrathecal [D-Ala2, Met5]enkephalinamide and [D-Ala2, D-Leu5]enkephalin (DADL) were equipotent, morphine and ethylketazocine were less potent, but nalorphine was inactive. A long-lasting, highly selective, mu-receptor antagonist, beta-funaltrexamine, blocked the inhibition of substance P behaviors by both morphine and ethylketazocine, but did not block the effect of DADL. These results suggest that spinal postsynaptic modulation of nociception is mediated by both delta-type and mu-type opioid agonists.

Animals↗
PubMed1982

Correlates of nociception and antinociception in dorsal root potentials in the rat.

The antinociceptive effectiveness of spinally administered opiates raises the question of their neural target in the spinal cord. A large body of evidence points to a site of action on primary afferent fibers before the first central synapse. The dorsal root potential (DRP) is a consequence of phasic presynaptic inhibitory action on the primary afferent fibers. In these studies in the rat, dorsal root potentials, evoked by non-noxious subcutaneous electrical stimulation, were altered by systemic and spinal administration of opiates and by two types of noxious stimulation. Noxious stimulation was accompanied by increased dorsal root potential amplitude, whereas antinociception was associated with decreased dorsal root potential amplitude. Treatment with morphine decreased the dorsal potential and blocked the increase in amplitude induced by noxious by noxious stimuli. These results indicate that nociception and antinociception differentially modulate the phasic component of presynaptic inhibition on primary afferent fibers in the spinal cord.

Analgesics↗
PubMed1982

Tail pinch induced consummatory behaviors are associated with analgesia.

Pinching the tail of a rat results in a set of consummatory behaviors including chewing, eating and licking. In the present study, the effect of tail pinch on pain thresholds was evaluated using the hot-plate and writhing tests. Continuous tail pinch resulted in chewing and markedly lengthened the latency to hind-paw licking and jumping (hot-plate test) when compared with control rats and totally eliminated writhing behaviors. Tail pinch (which induced chewing) for one minute prior to the analgesic testing also prolonged the latency of hot plate-induced behaviors and suppressed the number of writhing behaviors. Naloxone reversed the tail pinch induced analgesia as measured by the hot-plate test, but did not reverse tail pinch-induced analgesia as measured by the writhing test.

Analgesia↗
PubMed1980

Intrathecal morphine in mice: a new technique.

A simple, rapid technique for intrathecal injections by lumbar puncture in unanesthetized mice is described. Intrathecal [3H]morphine base was not found in significant quantities in either the midbrain or forebrain. Submicrogram quantities of morphine sulfate induced Straub tail response and tail-flick analgesia. These effects were dose related and antagonized by subcutaneous naloxone.

Analgesia↗
PubMed1978

Differential effects of spinal cord lesions on narcotic and non-narcotic suppression of nociceptive reflexes: further evidence for the physiologic multiplicity of pain modulation.

These studies examined the effects of bilateral lesions of the dorsolateral funiculus (DLF) of the rat spinal cord on the inhibition of a nociceptive reflex produced either by a systemic injection of 4 mg/kg of morphine or by a 20 sec exposure to 1.0 mA of transcutaneous electric shock. Reflex inhibition was quantified and analgesia inferred by use of a modified version of the D'Amour-Smith tail-flick test. Lesions which included only the DLF reduced morphine-produced analgesia (MA) by 73% but had no effect on shock-produced analgesia (SA) observed in the same rats. Baseline tail-flick latencies of this group were not affected by the lesions. Control lesions restricted to the dorsal columns attenuated neither MA nor SA. Lesions which included both the dorsal columns and DLF did not affect SA and produced no greater reduction in MA than lesions of the DLF alone. Previous work indicates that both MA and SA result, at least in part, from supraspinal activity. The current data indicate that: (1) supraspinal modulation participating in two different types of analgesic induction involves separate descending spinal pathways and (2) the maximal expression of analgesia produced by administration of narcotics requires the integrity of a supraspinal neural system projecting in the DLF.

Animals↗
PubMedDate not supplied

Spinal plasticity of acute opioid tolerance.

Spinal acute opioid tolerance remains mechanistically undercharacterized. Expanded clinical use of direct spinal administration of opioids and other analgesics indicates that studies to further understand spinal mechanisms of analgesic tolerance are warranted. Rodent models of spinal administration facilitate this objective. Specifically, acute spinal opioid tolerance in mice presents a plasticity-dependent, rapid, and efficient opportunity for evaluation of novel clinical agents. Similarities between the pharmacology of acute and chronic spinal opioid tolerance, neuropathic pain, and learning and memory suggest that this model may serve as a high through-put predictor of bioactivity of novel plasticity-modifying compounds.

Animals↗
PubMedDate not supplied

Intrathecal substance P and somatostatin in rats: behaviors indicative of sensation.

Biochemical, histochemical and neurophysiological data suggest that substance P and somatostatin are neurotransmitters for primary afferent neurons. This study used intrathecal administration of these peptides and others (neurotensin and vasoactive intestinal polypeptide) in chronically catheterized, environmentally adapted, freely moving rats to evaluate their effects on unconditioned behavior. Substance P and somatostatin each elicited behaviors which were dose related. The behaviors included caudally directed biting and licking along with hindlimb scratching, writhing and retching. The behavioral responses were rapid in onset (1 min) and, in the case of substance P, short in duration (3 min). Vehicle, neurotensin and vasoactive intestinal polypeptide were without effect. These results demonstrate the ability of substance P and somatostatin to induce behavior in rats upon intrathecal administration and extend previous studies in mice.

Animals↗
PubMedDate not supplied

Antinociceptive action of intrathecal neurotensin in mice.

Neurotensin has been demonstrated to be analgesic in rodents. This study used intrathecal injection of neurotensin in unanesthetized mice to evaluate the effect of the peptide at the spinal level on unconditioned behavior. Intrathecal administration of neurotensin produced dose-related inhibition of locomotor activity and of the response elicited by subcutaneous hypertonic saline. The effects of the peptide in the tail flick assay were variable and it produced no inhibition of the behavioral response to intrathecal substance P. The results indicate that neurotensin antinociception at the spinal level does not result from locomotor impairment, may be somewhat selective for chemically induced pain, and may be mediated by a presynaptic action on primary afferent fibers.

Animals↗
PubMedDate not supplied

Antinociception following implantation of AtT-20 and genetically modified AtT-20/hENK cells in rat spinal cord.

AtT-20 cells, which produce beta-endorphin, and AtT-20/hENK cells, which are AtT-20 cells transfected with a proenkephalin gene, were implanted in the rat spinal subarachnoid space in an effort to produce an antinociceptive effect. Host rats were tested for antinociceptive activity by standard nociceptive tests, tail flick and hot plate. Although cell implants had minimal effect on the basal response to thermal nociceptive stimuli, administration of the beta 2-adrenergic agonist isoproterenol produced antinociception in the cell-implanted group but not in the control group. The antinociceptive effect of isoproterenol was dose-related and could be blocked by the opioid antagonist naloxone. Immunohistochemical analysis of spinal cords revealed the presence of enkephalin-negative cells surrounding the spinal cord of rats receiving AtT-20 cell implants, and enkephalin-positive cells surrounding the spinal cord of rats receiving AtT-20/hENK cell implants. These results suggest that opioid-releasing cells implanted around rat spinal cord can produce antinociception and may provide an alternative therapy for chronic pain.

Animals↗
PubMedDate not supplied

Anti-nociceptive effect of tricyclic anti-depressants following intrathecal administration.

The anti-nociceptive effects of three tricyclic anti-depressants (desipramine, protriptyline, fluoxetine) were evaluated in mice following intrathecal administration. Nociceptive behavior was produced by intrathecal administration of Substance P and measured for 60 seconds following subcutaneous and intrathecal administration of vehicle and increasing doses of the drugs being tested. Systemically administered protriptyline produced dose related antinociception in this paradigm. A similar effect was seen following systemic desipramine; while fluoxetine was inactive systemically. Both protriptyline and desipramine given intrathecally were antinociceptive while fluoxetine had a biphasic effect, being analgesic only at low doses. These results indicate that tricyclic antidepressants may produce analgesia at the spinal level in rodents. This action may be related to the therapeutic success of tricyclic antidepressants in chronic pain syndromes.

Analgesics↗