The effect of galanin on WDR neuron activity in the spinal dorsal horn of rats 2001.pdf (original) (raw)
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The effect of galanin on wide-dynamic range neuron activity in the spinal dorsal horn of rats
Regulatory Peptides, 2001
. The present study investigated the effect of galanin on wide-dynamic range WDR neuron activity in the dorsal horn of the spinal cord of rats. The evoked discharge of WDR neurons was elicited by transdermic electrical stimulation applied on the ipsilateral hindpaw of rats. Galanin was administered directly on the spinal dorsal surface of L3-L5. The evoked discharge frequency of the WDR neurons decreased significantly after the administration of galanin and the effect lasted for more than 30 min. Furthermore, the inhibitory effect of galanin on the evoked discharge frequency of WDR neurons was blocked by following administration of the galanin antagonist galantide, indicating that the inhibitory effect of galanin on the activity of WDR neurons was induced by activating galanin receptors in the dorsal horn of the spinal cord. The results suggest that galanin has an inhibitory role in the transmission of presumed nociceptive information in the dorsal horn of the spinal cord in rats. q
Regulatory peptides, 2000
Galanin is a 29-amino acid peptide with a suggested role in nociception. The effect of galanin on wide-dynamic range neuron discharge frequency in rats with nerve ligation, used as a model of neurogenic pain, was investigated by extracellular recording methods. Seven to 14 days after sciatic nerve ligation, 0.1, 0.5 or 1 nmol of galanin was administered directly on the dorsal surface of the L3-L5 spinal cord of rats with sciatic nerve ligation. It was found that galanin inhibited the activity of wide-dynamic range neurons dose-dependently, an effect was more pronounced in sciatic nerve ligated rats than intact rats. Furthermore, when 1 nmol of galantide, the galanin antagonist, was administered on the dorsal surface of the L3-L5 spinal cord, the wide-dynamic range neuron discharge frequency increased significantly. The results suggest that galanin plays an important role in the modulation of presumed nociception in mononeuropathy.
Mechanisms of antinociception of spinal galanin: how does galanin inhibit spinal sensitization
Neuropeptides, 2005
Galanin by a spinal action has been shown to have an antihyperalgesic action. Thus, in rats with lumbar intrathecal (IT) catheters, the thermal hyperalgesia evoked by carrageenan paw injection was blocked by IT delivery of galanin 1-29 (Gal 1-29 ) and galanin 2-11 (Gal 2-11 ) with the rank order of activity being Gal 1-29 > Gal 2-11 . We sought to determine whether this spinal action reflects an effect upon afferent transmitter release, e.g., substance P (SP), and/or on secondary neurons, e.g., signaling postsynaptic to neurokinin 1 (NK1) receptor activation. To address the question on afferent release, we investigated the effect of IT administration of galanin on tissue injury-induced spinal NK1 internalization (an indicator of SP release). Noxious stimulation (paw compression) produced an increase in NK1 internalization in dorsal horn lamina I. IT pretreatment of rats with Gal 1-29 and Gal 2-11 significantly attenuated the evoked NK1 internalization, with the rank order of activity being Gal 1-29 > Gal 2-11 > saline. To address the question of postsynaptic action, we examined the effects of IT galanin upon IT SP-induced thermal hyperalgesia and spinal PGE 2 release. Application of SP (30 nmol) directly to spinal cord led to a decrease in thermal thresholds and a profound increase in PGE 2 concentration in spinal dialysates. Both phenomena were reversed by Gal 1-29 and Gal 2-11 (10 nmol, IT). These findings suggest that the antihyperalgesic effect of spinal galanin is due to its action on sites both presynaptic (inhibition of SP release) and postsynaptic (blockade of SP-evoked hyperalgesia and PGE 2 production) to the primary afferents.
Proceedings of The National Academy of Sciences, 2001
Galanin is a 29-aa neuropeptide with a complex role in pain processing. Several galanin receptor subtypes are present in dorsal root ganglia and spinal cord with a differential distribution. Here, we describe a generation of a specific galanin R2 (GalR2) agonist, AR-M1896, and its application in studies of a rat neuropathic pain model (Bennett). The results show that in normal rats mechanical and cold allodynia of the hindpaw are induced after intrathecal infusion of low-dose galanin (25 ng per 0.5 l͞h). The same effect is seen with equimolar doses of AR-M1896 or AR-M961, an agonist both at GalR1 and GalR2 receptors. In allodynic Bennett model rats, the mechanical threshold increased dose-dependently after intrathecal injection of a high dose of AR-M961, whereas no effect was observed in the control or AR-M1896 group. No effect of either of the two compounds was observed in nonallodynic Bennett model rats. These data indicate that a low dose of galanin has a nociceptive role at the spinal cord level mediated by GalR2 receptors, whereas the antiallodynic effect of high-dose galanin on neuropathic pain is mediated by the GalR1 receptors. Thus, a selective GalR1 agonist may be used to treat neuropathic pain. allodynia ͉ Bennett model ͉ dorsal root ganglia ͉ neuropeptide ͉ pain G alanin is a 29-aa (30 aa in humans) neuropeptide (1). It has a wide distribution in the nervous system and may be involved in a variety of physiological and pathophysiological activities (2), including pain signaling (3-5). Galanin is upregulated in dorsal root ganglion (DRG) neurons in many animal models based on peripheral nerve injury, including complete axotomy (6, 7), complete nerve constriction injury (8-10), as well as partial nerve ligation (9, 10). In agreement, enhanced immunoreactive galanin release was also found in the superficial dorsal horn ipsilateral to sciatic nerve injury (11).
Neuroscience Letters, 1990
The interaction between intrathecally (i.t.) applied galanin (GAL) and morphine was examined in electrophysiological and behavioural experiments. The physiological experiments were performed on decerebrate, spinalized, unanesthetized rats where the effects of i.t. GAL and morphine on the hamstring flexor reflex were studied. In the behavioural experiments sensitivity to noxious thermal stimulation was assessed on the hot plate test in rats injected with GAL and morphine via chronically implanted i.t. catheters. GAL at 100 ng in 10/tl, which by itself has no depressive effect, potentiated the depressive effect of morphine on the flexor reflex. In the behavioral study the same dose of GAL potentiated the antinociceptive effect of morphine on the hot plate test without having an analgesic effect by itself. It is suggested that GAL may enhance the analgesic effect of opiates in the spinal cord.
An interaction of opioids and galanin in dorsal horn of the spinal cord in mononeuropathic rats
Regulatory Peptides, 2000
The present study was performed in rats with experimentally induced mononeuropathy after common sciatic nerve ligation. The hind-paw withdrawal latencies to thermal and mechanical stimulation were increased significantly after intrathecal injection of 3 nmol of galanin. The increased hind-paw response latencies induced by galanin were attenuated by following intrathecal injection of 22 nmol, but not 11 or 2.75 nmol of the opioid receptor antagonist naloxone. Further, the increased hind-paw response latencies induced by galanin were prevented by following intrathecal injection of 10 nmol of mu-opioid receptor antagonist, beta-funaltrexamine (beta-FNA), but not by 10 nmol of delta-opioid receptor antagonist, natrindole or 10 nmol of kappa-opioid receptor antagonist, nor-binaltorphimine (nor-BNI). Intrathecal 10 nmol of beta-FNA alone had no significant effects on the hind-paw withdrawal responses. These results demonstrate the existence of a specific interaction between galanin and opioids in the transmission of presumed nociceptive information in the spinal cord of mononeuropathic rats. This interaction involves the activation of mu-opioid receptor.
Galanin receptor-expressing dorsal horn neurons: Role in nociception
Neuropeptides, 2011
Galanin, along with enkephalins and neuropeptide Y, has been hypothesized to negatively modulate nociception in the superficial dorsal horn of the spinal cord. In the present study, we sought to determine the role of presumably excitatory dorsal horn galanin receptor-expressing neurons in nociception by selectively destroying GalR1-expressing superficial dorsal horn interneurons using lumbar intrathecal injections of the targeted cytotoxin, galanin-saporin (Gal-sap). Lumbar intrathecal injection of Gal-sap (500 ng) reduced immunoperoxidase staining for GalR1 in the superficial dorsal horn without affecting primary afferent neurons in lumbar dorsal root ganglia. Lumbar intrathecal Gal-sap also: 1-reduced nocifensive reflex responding on the thermal plate at 0.3°C, 44°C, and 47°C; 2-increased hot side occupancy in a thermal preference task (15°C vs 45°C); and, 3-decreased escape from 44°C and 47°C, but not 20°C. Thus, similar to lesions of mu opiate receptor-expressing dorsal horn interneurons, selective destruction of GalR1-expressing superficial dorsal horn neurons produces heat hypo-algesia, likely due to loss of GalR1-expressing excitatory interneurons leading to reduced activation of nociceptive projection neurons in response to aversive heat. These results are different than those seen with intrathecal neuropeptide Y-saporin and suggest the potential value of selectively targeting GalR1-expressing dorsal horn neurons to control pain.
Galanin is contained in GABAergic neurons in the rat spinal dorsal horn
Neuroscience Letters, 1995
In order to determine which types of neuron in laminae I-III of the rat spinal dorsal horn contain the peptide galanin, pre-embedding immunocytochemistry with antiserum to galanin was combined with post-embedding detection of GABA-and glycine-like immunoreactivities. Sixty-eight galanin immunoreactive neurons in laminae I-III selected from four rats were examined, and in each case semi-thin sections through the cell body were tested with a monoclonal antibody to GABA and an antiserum to glycine. All of the 68 galanin-immunoreactive neurons tested were GABA-immunoreactive, while only one of them (in lamina III) was glycineimmunoreactive. This suggests that galanin is contained in inhibitory intemeurons, and that (like enkephalin, neuropeptide Y and thyrotropin-releasing hormone) it is mainly restricted to GABAergic neurons which do not use glycine as a co-transmitter.
The effects of intrathecal galanin and C-fiber stimulation on the flexor reflex in the rat
Brain Research, 1989
Galanin (GAL) was applied intrathecally (i.t.) at the lumbar level in decerebrate, spinalized, unanesthetized rats. GAL had no effect on the amplitude of the monosynaptic reflex over a wide concentration range, but at low concentrations if briefly facilitated the flexor reflex and at higher concentrations the facilitation was sometimes followed by a depression. GAL decreased the facilitatory effect of a conditioning stimulus train to C-fibers in the sural nerve. The depressive effect of GAL could be prevented by the i.t. coadministration of calcitonin gene-related peptide (CGRP), but not substance P (SP) and was not reversed by i.t. naloxone or bicuculline. The results illustrate the complex effect of GAL on the spinal cord, possibly exhibiting a biphasic effect. The observed effects on the flexor reflex are probably not due to changes in the excitability of motoneurons. Descending inhibitory pathways or local inhibitory non-GAL interneurons probably are not involved in the depressive effect of GAL. The possibility that the observed effects are related to primary sensory afferents containing not only GAL but also CGRP, and/or to local GAL neurons in the dorsal horn is discussed.
Brain Research, 2006
The expression of the galanin receptor-1 and-2 (Gal 1 and Gal 2) messenger ribonucleic acids (mRNAs) was studied in the lower spinal cord of rat by means of in situ hybridization, using ribonucleic acid probes (riboprobes). Naïve rats as well as rats with unilateral axotomy of the sciatic nerve or unilateral inflammation of the hindpaw were analyzed. In naïve rats, numerous Gal 1 mRNA-positive (+) neurons were detected in lamina (L) I-III. In addition, several Gal 1 mRNA + neurons were seen in deeper layers, including the ventral horns, area X, and the lateral spinal nucleus. In contrast, few and comparatively weakly labeled Gal 2 mRNA + neurons were observed, mostly in the ventral horns and in area X, with fewer in the dorsal horn and in the sympathetic and parasympathetic intermediate lateral cell columns. Axotomy induced a strong increase in intensity and number of Gal 2 mRNA + motoneurons ipsilateral to the lesion. In contrast, nerve cut or hindpaw inflammation did not alter the expression of Gal 1 or Gal 2 in the dorsal horn. The present (and previous) results suggest that galanin, acting through Gal 1 and Gal 2 receptors, has a modulatory role on spinal excitability, not only via interneurons in superficial dorsal horn, but also on neurons in deep layers and area X, as well as on the sympathetic and parasympathetic outflow. Furthermore, the nerve injury-induced Gal 2 upregulation in motor neurons suggests a role for galanin in survival/ regeneration mechanisms.