naloxone and Exophthalmos

Orexin A and B (hypocretin 1 and 2) are the endogenous ligands of orexin receptors, a G-protein-coupled orphan receptor family containing orexin 1 (OX1) and orexin 2 (OX2) types. Orexin A induces analgesia in acute and inflammatory pain models. We further elucidated the possible antiallodynic effect of intrathecal orexins in a rat model of postoperative pain. Mechanical allodynia was induced by incising the rat hind paw and evaluated with the withdrawal threshold to von Frey filament stimulation. Intrathecal orexin A (0.03-1 nmol) and orexin B (0.1-3 nmol) dose dependently attenuated the incision-induced allodynia. Orexin A (ED50 = 0.06 nmol) is more potent than orexin B. The effects of orexin A and B were abolished by their respective antibodies, but not by naloxone, and were attenuated by suramin and strychnine, the P2X purinergic and glycine receptor antagonists, respectively. SB-334867, an OX1 receptor antagonist, at 30 nmol completely blocked the effect of orexin A but, even at 100 nmol, only partially antagonized the effect of orexin B. Orexin A antibody, SB-334867, suramin, strychnine, or naloxone enhanced the incision-induced allodynic response. It is concluded that intrathecal orexins reduce incision-induced allodynia through OX1 receptors. Glycine and P2X purinergic receptors, but not opioid receptors, might be involved in the antiallodynic effects of orexins. Endogenous orexin might be released after incision injury to activate the spinal OX1 receptors as an endogenous analgesic protector.

Topics: Animals; Antibodies, Blocking; Benzoxazoles; Carrier Proteins; Exophthalmos; gamma-Aminobutyric Acid; Glycine Agents; Injections, Spinal; Intracellular Signaling Peptides and Proteins; Male; Naloxone; Naphthyridines; Narcotic Antagonists; Neuropeptides; Orexin Receptors; Orexins; Pain Threshold; Pain, Postoperative; Physical Stimulation; Rats; Rats, Wistar; Receptors, G-Protein-Coupled; Receptors, Glycine; Receptors, Neuropeptide; Receptors, Purinergic P2; Strychnine; Suramin; Synaptic Transmission; Urea

The influence of clonidine on the naloxone-induced withdrawal signs, escape attempts and precipitated shakes, was studied in morphine-dependent rats. Clonidine injected i.p. or intraventricularly (i. vent.) inhibited precipitated shakes and potentiated escape attempts induced by naloxone in morphine-dependent rats. Under pentobarbital anesthesia, precipitated shakes and ice water-induced wet shakes were inhibited by clonidine and norepinephrine. Clonidine injected i. vent. reduced body temperatures in morphine-dependent rats but not in placebo pellet-implanted rats. We suggest that clonidine modulates morphine withdrawal signs by potentiating the behavior associated with heat dissipation (escape attempts) and inhibiting the behavior associated with heat gain mechanisms (precipitated shakes). These effects may occur via stimulation of central noradrenergic mechanisms.

Topics: Anesthesia; Animals; Body Temperature; Cerebral Ventricles; Clonidine; Escape Reaction; Exophthalmos; Humans; Injections; Male; Morphine Dependence; Naloxone; Norepinephrine; Pentobarbital; Piloerection; Rats; Substance Withdrawal Syndrome; Time Factors; Tremor

Topics: Animals; Behavior, Animal; Blepharoptosis; Brain; Catalepsy; Catatonia; Electric Stimulation; Electrodes, Implanted; Exophthalmos; Haloperidol; Humans; Hypothalamus; Male; Morphine; Naloxone; Rats; Self Stimulation