Peripheral Pain Models Research Articles

Migraine and peripheral pain models show differential alterations in neuronal complexity.

ObjectiveOur laboratory has recently shown that there is a decrease in neuronal complexity in head pain processing regions in mouse models of chronic migraine‐associated pain and aura. Importantly, restoration of this neuronal complexity corresponds with anti‐migraine effects of known and experimental pharmacotherapies. The objective of the current study was to expand this work and examine other brain regions involved with pain or emotional processing. We also investigated the generalizability of our findings by analyzing neuronal cytoarchitectural changes in a model of complex regional pain syndrome (CRPS), a peripheral pain disorder.MethodsWe used the nitroglycerin (NTG) model of chronic migraine‐associated pain in which mice receive 10 mg/kg NTG every other day for 9 days. Cortical spreading depression (CSD), a physiological corelate of migraine aura, was evoked in anesthetized mice using KCl. CRPS was induced by tibial fracture followed by casting. Neuronal cytoarchitecture was visualized with Golgi stain and analyzed with Simple Neurite Tracer.ResultsIn the NTG model, we previously showed decreased neuronal complexity in the trigeminal nucleus caudalis (TNC) and periaqueductal gray (PAG). In contrast, we found increased neuronal complexity in the thalamus and no change in the amygdala or caudate putamen in this study. Following CSD, we observed decreased neuronal complexity in the PAG, in line with decreases in the somatosensory cortex and TNC reported with this model previously. In the CRPS model there was decreased neuronal complexity in the hippocampus, as reported by others; increased complexity in the PAG; and no change within the somatosensory cortex.ConclusionsCollectively these results demonstrate that alterations in neuronal complexity are a feature of both chronic migraine and chronic CRPS. However, each type of pain presents a unique cytoarchitectural signature, which may provide insight on how these pain states differentially transition from acute to chronic conditions.

EVALUATION OF ANALGESIC ACTIVITY OF SHOREA ROBUSTA RESINS

Shorea robusta (Sal), an important traditional Indian medicinal plant used in various ailments and rituals and the indigenous use of the resin of this plant as a medicament for treatment of various inflammatory conditions is well documented in literature. In the present study, ethanolic extract of S. robusta resin (SRE) was evaluated for its analgesic activity by making use of different central and peripheral pain models. The phytochemical studies have shown the presence of many secondary metabolites belonging to terpenoids, flavonoids, carbohydrate, lignans, phenols and sterols. Crude extracts and isolated compounds from Shorea robusta show a wide spectrum of pharmacological activities, such as anti-inflammatory, anti- obesity, antibacterial, wound healing, anti-pyretic & analgesic activities. Many studies have provided evidence for various traditional uses. The present review on its botany, traditional uses, pharmacological activities and phytochemistry which provides preliminary information for further studies for this potential medicinal plant. Pain is an unpleasant sensation and emotional experience linked to tissue damage. Pain occurs when something hurts, causing an unpleasant or uncomfortable feeling. The nearness of pain implies that something isn't right. Each individual is the best judge own pain. Pain of any origin comprises an individual’s life. The analgesic activity of SRE was assessed by employing different Materials and Methods: pain models such as, i) hot plate and tail flick tests for central analgesia.

OnabotulinumtoxinA exhibits greater efficacy compared to purified botulinum neurotoxin type A (BoNT/A-150 kDa) in peripheral pain models

OnabotulinumtoxinA exhibits greater efficacy compared to purified botulinum neurotoxin type A (BoNT/A-150 kDa) in peripheral pain models

Non-addictive orally-active kappa opioid agonists for the treatment of peripheral pain in rats

Addiction to conventional opioid pain analgesics is a major societal problem that is increasing at an alarming rate. New drugs to combat the effects of opioid abuse are desperately needed. Kappa-opioid agonists are efficacious in peripheral pain models but suffer from centrally-mediated effects. In this article, we discuss our efforts in developing peripheral kappa-based opioid receptor agonists that have the potential analgesic activity of opioids but do not manifest the negative side-effects of opioid use and abuse. Further, derivatives of the tetra-peptide D-Phe-D-Phe-D-Nle-D-Arg-NH2, such as CR665, exhibit high peripheral to central selectivity in analgesic models when administered intravenously (i.v.); however, they are inactive when administered orally. Application of our laboratory's proprietary non-natural amino acid technology to CR665 produced derivatives that exhibit peripheral analgesic activity when dosed orally but do not promote CNS-based effects. Lead compound JT09 activates the kappa-opioid receptor with EC50s in the low nM range, while agonist selectivity for kappa over other peripheral opioid receptors was >33,400 fold. Results indicate that JT09 is approximately as efficacious as morphine in alleviating peripheral pain, while failing to produce undesired CNS-mediated activity. Additionally, JT09 did not promote other CNS-mediated effects associated with morphine (addiction, sedation, dysphoria, tolerance, addiction). Thus, we propose that JT09 has potential for development as a novel analgesic. PerspectiveThis article presents data supporting the analgesic properties of an orally available, peripherally-restricted, kappa-opioid agonist for peripheral pain. A potential out-patient pharmaceutical that acts as efficacious as morphine in alleviating peripheral pain, while failing to produce undesired CNS-mediated effects, could help reduce the current health care burden associated with prescription opioids.

Evaluation of the analgesic efficacy of garlic shoots extract in experimental pain models in mice

Background: Garlic shoot and leaves are discarded as a waste material. Garlic has many properties like anti-inflammatory, anti-arthritic, anti-oxidant, dyslipidemic, anti-cancer, anti-infective therefore in the present study Garlic shoot extract (GSE) preparation was evaluated for its analgesic efficacy by making use of different central and peripheral pain models. So this study was performed using experimental central and peripheral pain models in mice. Methods: The analgesic efficacy of GSE was assessed by employing different pain models such as i)Hot plate and tail flick tests for central analgesia ii) 4% sodium chloride induced writhing as peripheral analgesic model . The percentage inhibition of writhes and prolongation of reaction time were the parameters of evaluation. The results obtained were analysed by ANOVA and Student’s unpaired “t”- test. Results: GSE treatment (250 mg/kg and 500 mg/kg) reduced writhing episodes significantly in 4%NaCl induced writhing in mice as compared to control indicating its analgesic effect. The highest percentage inhibition of pain was seen with 500mg/kg of GSE. GSE treatment, in Hot plate and Tail – flick methods significantly prolonged the reaction time at 90,120 minutes. Conclusions: Garlic shoot extract (GSE) was found to be effective in all three models of experimental pain. However it is less potent than standard analgesic drugs and could be employed safely in higher doses.

Spinal cord compression injury in lysophosphatidic acid 1 receptor‐null mice promotes maladaptive pronociceptive descending control

Although activation of the lysophosphatidic acid receptor 1 (LPA1) is known to mediate pronociceptive effects in peripheral pain models, the role of this receptor in the modulation of spinal nociception following spinal cord injury (SCI) is unknown. In this study, LPA1 regulation of spinal excitability mediated by supraspinal descending antinociceptive control systems was assessed following SCI in both wild-type (WT) and maLPA1-null receptor mice. The effect of a T8 spinal compression in WT and maLPA1-null mice was assessed up to 1 month after SCI using histological, immunohistochemical and behavioural techniques analysis including electrophysiological recording of noxious toes-Tibialis Anterior (TA) stimulus-response reflex activity. The effect of a T3 paraspinal transcutaneous electrical conditioning stimulus on TA noxious reflex temporal summation was also assessed. Histological analysis demonstrated greater dorsolateral funiculus damage after SCI in maLPA1-null mice, without a change in the stimulus-response function of the TA noxious reflex when compared to WT mice. While T3 conditioning stimulation in the WT group inhibited noxious TA reflex temporal summation after SCI, this stimulus strongly excited TA reflex temporal summation in maLPA1-null mice. The functional switch from descending inhibition to maladaptive facilitation of central excitability of spinal nociception demonstrated in maLPA1-null mice after SCI was unrelated to a general change in reflex activity. These data suggest that the LPA1 receptor is necessary for inhibition of temporal summation of noxious reflex activity, partly mediated via long-tract descending modulatory systems acting at the spinal level.

Analgesic activity of the ethanolic extract of Shorea robusta resin in experimental animals

Aim:Shorea robusta (Sal), an important traditional Indian medicinal plant used in various ailments and rituals and the indigenous use of the resin of this plant as a medicament for treatment of various inflammatory conditions is well documented in literature. In the present study, ethanolic extract of S. robusta resin (SRE) was evaluated for its analgesic activity by making use of different central and peripheral pain models.Materials and Methods:The analgesic activity of SRE was assessed by employing different pain models such as, i) hot plate and tail flick tests for central analgesia, ii) acetic acid- induced writhing (peripheral analgesic model), iii) formalin-induced hind paw licking (both central and peripheral model), iv) carrageenan-induced hyperalgesia (peripheral analgesic model) and v) post-surgical pain (peripheral analgesic model).Results:The extract produced significant central and peripheral analgesic effects, as is evident from increase in reaction time in hot plate and tail flick tests, inhibition in writhing counts in acetic acid-induced writhing test, inhibition of licking time in formalin-induced hind paw licking, increased pain threshold in paw withdrawal latency in carrageenan-induced hyperalgesia and increased paw withdrawal threshold in post-surgical pain.Conclusion:The results of the present study demonstrate marked antinociceptive effects of SRE.

A central neuropathic pain model by DSP-4 induced lesion of noradrenergic neurons: Preliminary report

Neuropathic pain models are classified as central and peripheral pain models. Although various peripheral neuropathic pain models are established, central pain models are based only on spinal cord injury. DSP-4 is a competitive inhibitor of norepinephrine uptake that selectively degenerates the locus coeruleus (LC)-noradrenergic neurons projection to the cerebral cortex and hippocampus. In the present study, we have tested whether lesion of LC-noradrenergic neurons by ip DSP-4 (0, 10, 30, 50 mg/kg, n = 7 each) could provide a new central neuropathic pain model in rats using a hot-plate and tail-flick tests. DSP-4 significantly reduced the hot-plate latency and norepinephrine contents especially in the coerulean regions. However, DSP-4 did not change tail-flick latency. There are significant correlations of the latency in the hot-plate test with norepinephrine contents in the cerebral cortex ( r = 0.432, p = 0.022), the hippocampus ( r = 0.465, p = 0.013) and the pons ( r = 0.400, p = 0.035) but not with those in the hypothalamus and the spinal cord. As response to hot-plate and tail-flick implies supra-spinal process and spinal reflex, respectively, central neuropathic pain may be facilitated by DSP-4 depleting LC-noradrenergic neurons although the present data are preliminary.