galantide and Pain

It has been demonstrated that galanin plays important roles in the modulation of nociceptive information in rats. The present study is performed to investigate the regulating role of galanin in nociception in the nucleus accumbens (NAc) of rats. Intra-NAc administration of galanin induces dose-dependent increases in the hindpaw withdrawal latency (HWL) to noxious thermal and mechanical stimulation in rats. Furthermore, the galanin-induced antinociceptive effects are blocked by following intra-NAc injection of the galanin receptor antagonist galantide. The results demonstrate that galanin induces antinociceptive effects in the NAc of rats, and galanin receptors are involved in the galanin-induced antinociception effects.

Topics: Analgesics; Animals; Galanin; Hot Temperature; Injections, Intraventricular; Male; Nucleus Accumbens; Pain; Pain Measurement; Physical Stimulation; Rats; Rats, Sprague-Dawley; Reaction Time; Receptors, Galanin; Substance P

Galanin (GAL) is suggested to be a neuropeptide involved in pain transmission. In this study we tried to determine, whether the increase of GAL concentration in brain cells affects impulse transmission between the motor centers localized in the vicinity of the third and fourth cerebral ventricles. The experiments were carried out on rats under chloralose anesthesia. The study objectives were realized using the method allowing to record the amplitude of evoked tongue jerks (ETJ) in response to noxious tooth pulp stimulation during the perfusion of the cerebral ventricles with solutions containing tested compounds. Perfusion of the cerebral ventricles with GAL concentration-dependently inhibited the ETJ amplitude. The antinociceptive effect of GAL was blocked by a galanin receptor antagonist, galantide (GLT) and by opioid antagonists: non-selective naloxone (Nal) and micro-selective beta-funaltrexamine (beta-FNA). In contrast, a delta-opioid receptor antagonist, naltrindole (NTI) or the kappa-opioid receptor antagonist, nor-binaltrophimine (nor-BNI) did not inhibit the effect of GAL. The antinociceptive effect of GAL was more pronounced when GAL was perfused in combination with other neuropeptides/neurohormones, such as endomorphin-2 (EM-2), vasopressin (AVP) and oxytocin (OT). The present results demonstrate that in the orofacial area analgesic activity is modulated by GAL, OT and AVP and that EM-2-induced antinociception involves GAL.

Topics: Animals; Arginine Vasopressin; Cerebral Ventricles; Dental Pulp; Electric Stimulation; Galanin; Hypoglossal Nerve; Male; Narcotic Antagonists; Oligopeptides; Oxytocin; Pain; Pain Measurement; Perfusion; Rats; Rats, Long-Evans; Reflex; Substance P; Tongue; Trigeminal Nerve

We investigated the peripheral function of galanin (GAL) in capsaicin (CAP)-induced inflammatory pain. Intraplantar GAL (0.1 ng/microl) alone does not produce nociceptive behaviors. However, ipsilateral but not contralateral GAL at low doses (0.1 ng/microl) significantly increases CAP-evoked nociceptive behaviors approximately twofold. This effect is attributed to activation of peripheral GAL receptor 2 (GalR2) because a selective GalR2 agonist (AR-M1896) mimics the pro-nociceptive actions of GAL. Recording from nociceptors confirms that GAL does not modify activity of nociceptors but markedly enhances CAP-induced excitation of these fibers. CAP produces a discharge rate of 0.15+/-0.05 impulses/s which increases to 0.54+/-0.17 impulses/s following CAP+GAL. Immunohistochemical studies indicate GalR2 are highly expressed (65.8%) in L5 dorsal root ganglion (DRG) cells. Also, 44.5% GalR2-positive DRG neurons label for the capsaicin receptor (vanilloid receptor 1, VR1) while 61.7% of VR1-positive DRG neurons label for GalR2; 28.1% of total DRG neurons are double-labeled supporting the hypothesis that GAL-induced effects are mediated by GalR2 on capsaicin-sensitive primary afferents. Furthermore, 68.0% unmyelinated and 23.1% myelinated digital nerve axons label for GalR2, indicating the receptor is transported out to the periphery. Immunostaining for GAL peptide in digital nerves labels 46.4% unmyelinated and 27.1% myelinated axons, suggesting that afferents are a major source of ligand for peripheral GalR2. These results suggest that peripheral GAL has an excitatory role in inflammatory pain, likely mediated by peripheral GalR2 and that GAL can modulate VR1 function.

Topics: Action Potentials; Animals; Axons; Behavior, Animal; Capsaicin; Cell Count; Dose-Response Relationship, Drug; Drug Interactions; Galanin; Immunohistochemistry; In Vitro Techniques; Inflammation; Male; Microscopy, Electron; Pain; Pain Measurement; Peptide Fragments; Peripheral Nerves; Rats; Rats, Sprague-Dawley; Receptor, Galanin, Type 2; Receptors, Drug; Skin; Substance P

Although the tuberomammillary nucleus (TM) is well defined in terms of anatomy and neurochemistry, little is known about its function in nociceptive modulation. There was an abundance of galanin-immunoreactive fibers in the TM, and galanin has been implicated in pain processing. The present study assessed the role of galanin in the modulation of nociception in the TM of rats. Intra-TM injection of galanin dose-dependently increased the hindpaw withdrawal latency of rats to a noxious thermal stimulus, indicating an antinociceptive role of galanin in the TM. The antinociceptive effect of galanin was blocked by a subsequent intra-TM injection of galantide, a putative galanin receptor antagonist, suggesting that the antinociceptive effect of galanin is mediated by galanin receptors. Moreover, there was abundant galanin receptor 1 (GalR1) in the TM, and the number of GalR1-positive neurons in the ipsilateral TM increased significantly after unilateral loose ligation of the sciatic nerve compared with the contralateral TM or the TM of intact rats. However, the number of GalR1-positive neurons was not significantly altered by carrageenan-induced inflammation, in either the ipsilateral or the contralateral TM. The results suggest that galanin and GalR1 in the TM may play important roles in pain regulation.

Topics: Analysis of Variance; Animals; Carrageenan; Dose-Response Relationship, Drug; Functional Laterality; Galanin; Hyperalgesia; Hypothalamic Area, Lateral; Immunohistochemistry; Male; Neuronal Plasticity; Pain; Pain Measurement; Physical Stimulation; Rats; Rats, Wistar; Reaction Time; Receptors, Galanin; Sciatic Neuropathy; Substance P; Time Factors

Galanin, a 29 amino acid peptide, has been reported to possess antinociceptive properties at the spinal site and to potentiate opioid-induced antinociception. Our aim was to investigate whether also endogenous galanin interacts with an exogenously administered opioid, morphine, in the rat spinal cord. This question was investigated by use of the recently developed galanin receptor antagonists galantide [M-15, galanin-(1-13)-substance P-(5-11) amide] and M-35 [galanin-(1-13)-bradykinin-(2-9) amide]. Nociception was assessed in the rat tail-flick test using radiant heat and the rat Randall-Selitto model of inflammatory pain using vocalization as the nociceptive criterion. Intrathecal (i.t.) injections were performed in rats under either anaesthesia. Morphine was administered either i.t. or intraperitoneally (i.p.), and the antagonists were injected i.t. [125I]Galanin binding experiments were performed on crude synaptosomal membranes of the rat spinal cord. In the rat tail-flick test, i.t. injection of 3 micrograms morphine evoked antinociception of about 75% of the maximal possible effect (% MPE). Co-injection of either 2 micrograms galantide or 2 micrograms M-35 with morphine almost completely abolished the antinociceptive effect of morphine. I.p. injection of 2.15 mg/kg morphine elicited about 80% MPE when given 10 min prior to i.t. saline injection. Injection of the antagonists instead of saline antagonised the antinociceptive effect of morphine partially thus showing the spinal proportion of the overall antinociceptive effect. In the rat Randall-Selitto test, 3 micrograms morphine, injected i.t., produced antinociception of almost 100% MPE.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Binding Sites; Bradykinin; Galanin; Injections, Spinal; Male; Morphine; Pain; Peptide Fragments; Peptides; Rats; Rats, Sprague-Dawley; Receptors, Galanin; Receptors, Gastrointestinal Hormone; Spinal Cord; Substance P; Synaptic Membranes