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Query: UMLS:C0423716 (Neuropathic pain)
 1,417 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neuropathic pain responds poorly to opioids. We now report that combination of systemic morphine (2 mg/kg) and dextromethorphan (45 mg/kg), a clinically available antitussive with NMDA-antagonist properties, markedly alleviated mechanical and cold allodynia-like behavior in a rat model of peripheral mononeuropathy. Neither drug produced a significant effect on its own at these doses. The anti-allodynic effect of morphine plus dextromethorphan was reversed by naloxone. The present results suggest that a combination of NMDA-antagonist and opiates might be effective in treating neuropathic pain. Furthermore, the effect of this drug combination is mainly mediated via opioid receptors.
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PMID:Dextromethorphan potentiates the effect of morphine in rats with peripheral neuropathy. 960 69

The usefulness of sensory symptoms in the assessment of diabetic polyneuropathy is unclear. In the present study, we studied the hypothesis that pain is associated with small nerve fibre function, and that sensory alteration is associated with large nerve fibre function. In addition, we assessed the reproducibility and the ability to detect changes in clinical status over time of the nerve function tests currently used in clinical trials. Patients (78) with stable diabetic polyneuropathy were examined on three separate occasions with a test-retest interval of 17 and 52 weeks. Small nerve fibre function was measured using temperature discrimination thresholds for warmth (TDTwarmth) and cold (TDTcold). Large nerve fibre function was measured by testing sensory and motor nerve conduction velocities (SNCV and MNCV) and vibration perception thresholds (VPT). Neuropathic pain was only significantly associated with TDTcold, and with the MNCV of the tibial nerve. Sensory alteration was associated with almost all nerve function tests except the SNCV and MNCV of the ulnar nerve. The measurements of symptom severity and the nerve function tests all proved to be sufficiently reproducible. The standardized smallest detectable difference on group level (SDD) of the measurement of sensory alteration and neuropathic pain were almost the same (9% and 12%, respectively). Among the nerve function tests, the SNCV and MNCV had the smallest SDD (3-4%), and were, therefore, potentially the most responsive instruments. The SDD of the TDT was greater than the VPT (9-14% vs 21-28%, respectively). In conclusion, neuropathic pain was not associated with small nerve fibre function, and sensory alteration was associated with both large and small fibre function. In addition, the standardized measurement of symptom severity, the SNCV and MNCV tests, and the VPT test appear to be useful for monitoring the course of polyneuropathy in clinical trials.
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PMID:Methods for assessing diabetic polyneuropathy: validity and reproducibility of the measurement of sensory symptom severity and nerve function tests. 1067 Sep 7

Neuropathic pain, due to peripheral nerve damage, can include allodynia (perception of innocuous stimuli as being painful), hyperalgesia (increased sensitivity to noxious stimuli) and spontaneous pain, often accompanied by sensory deficits. Plasticity in transmission and modulatory systems are implicated in the underlying mechanisms. The Kim and Chung rodent model of neuropathy (Kim and Chung, Pain 50 (1992) 355) employed here involves unilateral tight ligation of two (L5 and L6) of the three (L4, L5, and L6) spinal nerves of the sciatic nerve and reproducibly induced mechanical and cold allodynia in the ipsilateral hindpaw over the 14 day post-operative period. In vivo electrophysiological techniques have then been used to record the response of dorsal horn neurones to innocuous and noxious electrical and natural (mechanical and thermal) stimuli after spinal nerve ligation (SNL). Activation of voltage-dependent calcium channels (VDCCs) is critical for neurotransmitter release and neuronal excitability, and antagonists can be antinociceptive. Here, for the first time, the effect of N- and P-type VDCC antagonists (omega-conotoxin-GVIA and omega-agatoxin-IVA, respectively) on the evoked dorsal horn neuronal responses after neuropathy have been investigated. Spinal omega-conotoxin-GVIA (0.1-3.2 microg) produced prolonged inhibitions of both the electrically- and low- and high-intensity naturally-evoked neuronal responses in SNL and control rats. Spinal omega-agatoxin-IVA (0.1-3.2 microg) also had an inhibitory effect but to a lesser extent. After neuropathy the potency of omega-conotoxin-GVIA was increased at lower doses in comparison to control. This indicates an altered role for N-type but not P-type VDCCs in sensory transmission after neuropathy and selective plasticity in these channels after nerve injury. Both pre- and post-synaptic VDCCs appear to be important.
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PMID:Effects of spinally delivered N- and P-type voltage-dependent calcium channel antagonists on dorsal horn neuronal responses in a rat model of neuropathy. 1132 45

Paclitaxel, an effective anti-neoplastic agent in the treatment of solid tumors, produces a dose-limiting painful peripheral neuropathy in a clinically significant number of cancer patients. Prior work has demonstrated paclitaxel-induced neurodegeneration and sensory loss in laboratory rodents. We describe here an experimental paclitaxel-induced painful peripheral neuropathy. Adult male rats were given four intraperitoneal injections on alternate days of vehicle or 0.5, 1.0, or 2.0 mg/kg of paclitaxel (Taxol). Behavioral tests for pain using mechanical and thermal stimuli applied to the tail and hind paws, and tests for motor performance, were taken before, during and after dosing for 22-35 days. All three doses of paclitaxel caused heat-hyperalgesia, mechano-allodynia, mechano-hyperalgesia, and cold-allodynia, but had no effect on motor performance. Neuropathic pain began within days and lasted for several weeks. We did not detect any dose-response relationship. Tests at the distal, mid, and proximal tail failed to show evidence of a length-dependent neuropathy. Vehicle control injections had no effect on any measure. No significant systemic toxicities were noted in the paclitaxel-treated animals. Light-microscopic inspection of the sciatic nerve (mid-thigh level), L4-L5 dorsal root ganglia, and dorsal and ventral roots, and the gray and white matter of the L4-L5 spinal cord, showed no structural abnormalities. Electron microscopic examination of the sciatic nerve (mid-thigh level) and the L4-L5 dorsal root ganglia and dorsal horns demonstrated no degeneration of myelinated and unmyelinated axons in the sciatic nerve and roots, but revealed endoneurial edema. This model may be useful in understanding a significant source of pain in cancer patients, and in finding ways to avoid the neurotoxicity that limits paclitaxel therapy.
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PMID:A painful peripheral neuropathy in the rat produced by the chemotherapeutic drug, paclitaxel. 1173 Oct 66

Neuropathic pain (characterized by hyperalgesia and allodynia to mechanical and thermal stimuli) causes cellular changes in spinal dorsal horn neurons, some of which parallel those in synaptic plasticity associated with learning. Ubiquitin C-terminal hydrolase (UCH) appears to play a key role in long-term facilitation in Aplysia. The cooperation of UCH with the proteolytic enzyme complex known as the proteasome is required for the degradation of a number of signaling molecules within the cell that may remove normal restraints on synaptic plasticity. We have used electrophysiology, in situ hybridization histochemistry, semiquantitative RT-PCR, Western blotting, and in vivo behavioral reflex analysis to investigate the ubiquitin-proteasome system in a model of neuropathic pain. In neuropathic animals, ionophoretic application of selective proteasome inhibitors attenuated dorsal horn neuron firing evoked by normally innocuous brush or cold stimuli and by noxious mustard oil stimuli. In control animals, only mustard oil-evoked responses were inhibited. Intrathecal administration of proteasome inhibitors attenuated hyperalgesia and allodynia in neuropathic rats. Expression of UCH-L1 (a rat homolog of Aplysia neuronal UCH and of the human UCH-L1, also known as PGP 9.5) and its mRNA were selectively increased within the ipsilateral dorsal horn of neuropathic rats, supporting the idea of a role for the ubiquitin-proteasome system in nociceptive processing. Proteasome inhibitors selectively attenuate allodynic and hyperalgesic responses in neuropathic pain, with some reduction in normal nociceptive, but not non-nociceptive responses, and potentially represent a novel therapeutic strategy for neuropathic pain.
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PMID:A role of the ubiquitin-proteasome system in neuropathic pain. 1185 Apr 63

Co-localization of opioid and melanocortin receptor expression, especially at the spinal cord level in the dorsal horn and in the gray matter surrounding the central canal led to the suggestion that melanocortins might play a role in nociceptive processes. In the present studies, we aimed to determine the effects of melanocortins, administered intrathecally, on allodynia, and to ascertain whether there is an interaction between opioid and melanocortin systems at the spinal cord level. Neuropathic pain was induced by chronic constriction injury (CCI) of the right sciatic nerve in rats. Tactile allodynia was assessed using von Frey filaments, while thermal hyperlagesia was evaluated in cold water allodynia test. In the present experiments, melanocortin receptor antagonist, SHU9119 was much more potent than mu-opioid receptor agonist, morphine after their intrathecal (i.th.) administration in neuropathic rats. SHU9119 alleviated allodynia in a comparable manner to DAMGO, a selective and potent mu-opioid receptor agonist. Administration of melanocortin receptor agonist, melanotan-II (MTII) increased the sensitivity to tactile and cold stimulation. Moreover, we demonstrated that the selective blockade of mu-opioid receptor by cyprodime (CP) enhanced antiallodynic effect of SHU9119 as well as pronociceptive action of MTII, whereas the combined administration of mu receptor agonist (DAMGO) and SHU9119 significantly reduced the analgesic effect of those ligands. DAMGO also reversed the proallodynic effect of melanocortin receptor agonist, MTII. In conclusion, it seems that the endogenous opioidergic system acts as a functional antagonist of melanocortinergic system, and mu-opioid receptor activity appears to be involved in the modulation of melanocortin system function.
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PMID:Modulation of melanocortin-induced changes in spinal nociception by mu-opioid receptor agonist and antagonist in neuropathic rats. 1249 47

Neuropathic pain is caused by injury of the peripheral or central nervous system. The neurological examination of the sensory system in neuropathic pain patients guides the anatomical localization of the injury. Among the sensory modalities to be tested, priority should be given to those subserved by small peripheral sensory fibers or by the spinothalamic tract that most commonly are abnormal in neuropathic pain patients. Testing of cold and warm perception was traditionally carried out in the clinic using tubes filled with water at different temperatures, a cumbersome method that has limited the routine examination of these sensory modalities. The Lindblom roller offers a practical and effective method of readily testing temperature perception and is among the best available clinical tools for delineating the anatomical boundaries of a sensory abnormality. Routinely use of the Lindblom roller shall be standard bedside clinical assessment of neuropathic pain patients. To exemplify this statement we describe two patients affected by complex and fluctuating painful sensory abnormalities caused by an extradural mass compressing the spinal cord. The level of the injury was readily localized with a roller kept at room temperature.
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PMID:The Lindblom roller. 1282 7

Neuropathic pain is one of the important microvascular complications of diabetes. Oxidative stress and superoxide play a critical role in the development of neurovascular complications in diabetes. Aim of the present study was to evaluate the effect of quercetin, a bioflavonoid on thermal nociceptive responses in streptozotocin (STZ)-induced diabetic rats assessed by tail-immersion and hot plate methods. After 4-weeks of a single intravenous STZ injection (45 mg/kg body weight), diabetic rats exhibited a significant thermal hyperalgesia and cold allodynia along with increased plasma glucose and decreased body weights as compared with control rats. Chronic treatment with quercetin (10 mg/kg body weight; p.o) for 4-weeks starting from the 4th week of STZ-injection significantly attenuated the cold allodynia as well as hyperalgesia. Results indicate that quercetin, a natural antioxidant, may be helpful in diabetic neuropathy.
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PMID:Quercetin attenuates thermal hyperalgesia and cold allodynia in STZ-induced diabetic rats. 1557 24

Patients with neuropathic pain present a clinical challenge. Neuropathic pain, when chronic, often leads to disability. Diagnosis can be difficult because both positive and negative sensory and motor signs and symptoms may be present, as well as a variety of comorbid conditions. In addition, there may be a high degree of interpatient variability. Currently, clinical evaluation, rather than diagnostic tests, is one of the best available tools for assessment and diagnosis. As with all chronic pain conditions, the key to a thorough assessment is a thorough history that includes medical, functional, and psychosocial evaluations. Currently available pain assessment tools, which are widely used in nursing practice, are still inadequate for use in patients with neuropathic pain. The physical and neurologic examination remains a critical element for patient evaluation. This includes an assessment of spontaneous pain (continuous or intermittent), pain evoked by daily activities (allodynia), and other abnormal sensations that are not necessarily painful (paresthesias, dysesthesias). Sensitivity to pinprick, touch, pressure, cold, heat, and vibration are measured, often confirming the suspected diagnosis. Patients may be confused by the unusual sensations they are experiencing and unable to effectively describe or communicate their symptoms. This communication barrier may contribute to an inadequate physical examination. With improved skills in patient assessment and through enhanced communication with patients, nurses can make an important contribution to treatment outcomes in patients with neuropathic pain.
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PMID:Neuropathic pain: a guide to comprehensive assessment. 1564 55

Neuropathic pain is a clinical manifestation characterized by the presence of spontaneous pain, allodynia and hyperalgesia. Here, we have evaluated the involvement of CB1 cannabinoid receptors in the development and expression of neuropathic pain. For this purpose, partial ligation of the sciatic nerve was performed in CB1 cannabinoid receptor knockout mice and their wild-type littermates. The development of mechanical and thermal allodynia, and thermal hyperalgesia was evaluated by using the von Frey filaments, cold-plate and plantar tests, respectively. Pre-surgical tactile and thermal withdrawal thresholds were similar in both genotypes. In wild-type mice, sciatic nerve injury led to a neuropathic pain syndrome characterized by a marked and long-lasting reduction of the paw withdrawal thresholds to mechanical and thermal stimuli. These manifestations developed similarly in mice lacking CB1 cannabinoid receptors. We have also investigated the consequences of gabapentin administration in these animals. Gabapentin (50 mg/kg/day, i.p.) induced a similar suppression of mechanical and thermal allodynia in both wild-type and CB1 knockout mice. Mild differences between genotypes were observed concerning the effect of gabapentin in the expression of thermal hyperalgesia. Taken together, our results indicate that CB1 cannabinoid receptors are not critically implicated in the development of neuropathic pain nor in the anti-allodynic and anti-hyperalgesic effects of gabapentin in this model.
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PMID:Development and expression of neuropathic pain in CB1 knockout mice. 1616 63


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