The therapeutic potential of galanin in the management of pain - a review article.

Neuropeptides represent the most diverse family of neurotransmitters counting numerous members and even more G protein-coupled receptors, all of which are potential targets for drug development. Here, we focus on galanin and its three receptors by describing their possible involvement in pain and regeneration. Although animal experiments indicate that galanin, together with other molecules, may act as an endogenous system protecting against pain and improving nerve growth, these results have so far not been translated into patient treatments.

Sinomenine facilitates the efficacy of gabapentin or ligustrazine hydrochloride in animal models of neuropathic pain.

Management of chronic pain is restricted by the lack of effective tools. This study evaluated the efficacies of sinomenine combined gabapentin or ligustrazine hydrochloride in treating peripheral and central chronic neuropathic pain. The study was conducted in mice with photochemically induced sciatic nerve injury, and in rats with photochemically induced spinal cord injury.

Exploring the transcriptome of resident spinal microglia after collagen antibody-induced arthritis.

Recent studies have suggested a sexually dimorphic role of spinal glial cells in the maintenance of mechanical hypersensitivity in rodent models of chronic pain. We have used the collagen antibody-induced arthritis (CAIA) mouse model to examine differences between males and females in the context of spinal regulation of arthritis-induced pain. We have focused on the late phase of this model when joint inflammation has resolved, but mechanical hypersensitivity persists.

Gabapentin and NMDA receptor antagonists interacts synergistically to alleviate allodynia in two rat models of neuropathic pain.

Background and aims The clinical management of neuropathic pain remains a challenge. We examined the interaction between gabapentin and NMDA receptor antagonists dextromethrophan and MK-801 in alleviating neuropathic pain-like behaviors in rats after spinal cord or sciatic nerve injury. Methods Female and male rats were produced with Ischemic spinal cord injury and sciatic nerve injury.

Repeated sinomenine administration alleviates chronic neuropathic pain-like behaviours in rodents without producing tolerance.

Background and aims We have previously reported that systemic administration of sinomenine produced antinociception in various experimental pain conditions in rodents, particularly in models of neuropathic pain. In the present study we assessed the effects of repeated administration of sinomenine in two rodent models of neuropathic pain in order to study the development of tolerance. Methods The analgesic effect of sinomenine was tested in female Sprague-Dawley rats that exhibited mechanical and cold hypersensitivity following ischaemic injury to the spinal cord and in male C57/BL6 mice that developed mechanical hypersensitivity after ischaemic injury to the sciatic nerve.

Sinomenine alleviates mechanical hypersensitivity in mice with experimentally induced rheumatoid arthritis.

Background and aims We have previously reported that sinomenine, an alkaloid isolated from the root of the plant Sinomenium acutum, had antinociceptive effect in rodent models of acute inflammatory or neuropathic pain. As a traditional medicine, sinomenine is used in China to treat rheumatoid arthritis (RA). Methods In the present study, we evaluated the potential antinociceptive effect of sinomenine in a mouse model of RA, collagen type II antibody (CII Ab) induced arthritis (CAIA) after acute and chronic administration.

Phenotypic changes in dorsal root ganglion and spinal cord in the collagen antibody-induced arthritis mouse model.

The mechanisms underlying rheumatoid arthritis (RA)-induced pain are still not fully elucidated, and accumulating data indicate that peripheral inflammation is not the only factor driving pain in these patients. The focus of our work is to investigate the molecular basis for long-term alterations in nociceptive pathways induced by polyarthritis using the collagen antibody-induced arthritis (CAIA) mouse model. In this model, mechanical hypersensitivity outlasts the joint inflammation by weeks.

N-terminal truncations of substance P 1-7 amide affect its action on spinal cord injury-induced mechanical allodynia in rats.

Central neuropathic pain can arise from injury of the spinal cord and can become chronic. Treatment is difficult and, because complete pain relief is currently very hard to achieve, there is a need for new, more effective treatment options. In this study we used an animal model of spinal cord injury to evaluate the potency of a bioactive fragment of substance P (SP), i.

Quantitative test of responses to thermal stimulation in spinally injured rats using a Peltier thermode: a new approach to study cold allodynia.

In this work, we described a method of testing of responses of spinally injured rats to thermal stimulation (heating and cooling) to the flank area using a Peltier thermode. With a baseline holding temperature at 32°C and the temperature change rate of 0.5°C/s, we measured vocalization thresholds of rats to thermal stimulation in the flank area.

Meteorin reverses hypersensitivity in rat models of neuropathic pain.

Neuropathic pain is caused by a lesion or disease to the somatosensory nervous system and current treatment merely reduces symptoms. Here, we investigate the potential therapeutic effect of the neurotrophic factor Meteorin on multiple signs of neuropathic pain in two distinct rat models. In a first study, two weeks of intermittent systemic administration of recombinant Meteorin led to a dose-dependent reversal of established mechanical and cold hypersensitivity in rats after photochemically-induced sciatic nerve injury.

Genetic and sex influence on neuropathic pain-like behaviour after spinal cord injury in the rat.

Background: Chronic pain of neuropathic nature after spinal cord injury (SCI) is common and its underlying mechanisms are poorly understood. Genes, as well as sex, have been implicated, but not thoroughly investigated in experimental genetic models for complex traits. We have previously found that inbred Dark-Agouti (DA) rats develop more severe SCI pain-like behaviour than a major histocompatibility complex-congenic Piebald Virol Glaxo (PVG)-RT1(av1) strain in a model of photochemically induced SCI.

Heparanase overexpression reduces carrageenan-induced mechanical and cold hypersensitivity in mice.

Heparanase controls the structure and functions of extracellular matrix (ECM) by degrading heparan sulfate proteoglycans. Heparanase is involved in inflammatory process through modulating the functions of inflammatory cytokines. The present study aimed to find out whether overexpression of heparanase in mice affects carrageenan-induced localized inflammation and inflammatory hyperalgesia.

Essential role of Ret for defining non-peptidergic nociceptor phenotypes and functions in the adult mouse.

Transduction of pain following noxious stimuli is mediated by the activation of specialized ion channels and receptors expressed by nociceptive sensory neurons. A common early nociceptive sublineage expressing the nerve growth factor receptor TrkA diversifies into peptidergic and non-peptidergic nociceptors around birth. In this process, peptidergic neurons maintain TrkA expression, while non-peptidergic neurons downregulate TrkA and upregulate the common glial-derived neurotrophic factor family ligand receptor Ret and bind the isolectin B4 (IB4).

Galanin and spinal pain mechanisms: past, present, and future.

Since the discovery of galanin in 1983, one of the most frequently suggested physiological function for this peptide is pain modulation at the level of the spinal cord. This notion, initially based on the preferential distribution of galanin in dorsal spinal cord, has been supported by results from a large number of morphological, molecular, and functional studies. It is generally agreed that spinally applied galanin produces a biphasic, dose-dependent effect on spinal nociception through activation of GalR1 (inhibitory) or GalR2 (excitatory) receptors.

Peripheral adenosine A2A receptors are involved in carrageenan-induced mechanical hyperalgesia in mice.

Here we studied the role of peripheral adenosine A(2A) receptors in mechanical hyperalgesia during inflammation using mice lacking the A(2A) receptors. Unilateral s.c.

Expression of DRG candidate pain molecules after nerve injury--a comparative study among five inbred mouse strains with contrasting pain phenotypes.

Neuropathic pain that develops after trauma to a nerve may be caused by altered transcription of genes in the damaged neurons. We have previously investigated the effect of nerve injury on the expression of six dorsal root ganglion (DRG) pain candidate molecules in five inbred mouse strains with different pain phenotypes after nerve injury. In this study, we present a detailed morphological examination of mRNA expression in the DRG in the same mouse strains.

Sex differences in the development of localized and spread mechanical hypersensitivity in rats after injury to the infraorbital or sciatic nerves to create a model for neuropathic pain.

Background: Neuropathic pain after injury to the nervous system is a difficult clinical problem. Sex differences in the development of neuropathic pain have not been well established experimentally or clinically.

Objective: Rats were used to examine sex differences in localized and spread mechanical hypersensitivity after partial injury to their infraorbital or sciatic nerves in a model of neuropathic pain.

Multipotent mesenchymal stromal cells attenuate chronic inflammation and injury-induced sensitivity to mechanical stimuli in experimental spinal cord injury.

Purpose: Previous reports established that after a contusion injury to the rat spinal cord, locomotor function was enhanced by the transplantation of cells from bone marrow referred to as either mesenchymal stem cells or multipotent mesenchymal stromal cells (MSCs). It has also been established that neural stem cells (NSCs) enhance locomotor function after transplantation into the injured rat spinal cord. However, the beneficial effects of NSCs are limited by graft-induced allodynia-like responses.

Autotomy behavior correlates with the DRG and spinal expression of sodium channels in inbred mouse strains.

Patients who have suffered nerve injury show profound inter-individual variability in neuropathic pain even when the precipitating injury is nearly identical. Variability in pain behavior is also observed across inbred strains of mice where it has been attributed to genetic polymorphisms. Identification of cellular correlates of pain variability across strains can advance the understanding of underlying pain mechanisms.

Ablation of estrogen receptor alpha or beta eliminates sex differences in mechanical pain threshold in normal and inflamed mice.

We examined nociceptive responses to mechanical stimulation in mice of both sexes lacking the estrogen receptor alpha or beta and in respective wild types under normal conditions, after inflammation of a hindpaw or peripheral nerve injury. In normal wild-type mice, females had significantly lower paw withdrawal threshold than males. There was no significant difference between wild-type mice and knock-outs of either estrogen receptor alpha or beta in mechanical response threshold in male mice.

Correlational analysis for identifying genes whose regulation contributes to chronic neuropathic pain.

Background: Nerve injury-triggered hyperexcitability in primary sensory neurons is considered a major source of chronic neuropathic pain. The hyperexcitability, in turn, is thought to be related to transcriptional switching in afferent cell somata. Analysis using expression microarrays has revealed that many genes are regulated in the dorsal root ganglion (DRG) following axotomy.