Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0423716 (Neuropathic pain)
 1,417 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The aim of this study was to evaluate the influence of age and gender on pain characteristics and opioid response in advanced cancer patients followed at home. A perspective study was carried out in a sample of 181 consecutive advanced cancer patients who required opioids in the last 4 weeks before death. Pain intensity and symptoms associated with opioid therapy at weekly intervals for 4 weeks were recorded, as were the previous oncological treatments. Opioid doses increased over time, but remained stable in the last 2 weeks of life, while pain intensity decreased over time despite unchanged use of NSAIDs. A considerable increase in symptom intensity was observed in the last weeks of life, except for nausea and vomiting. Visceral pain was more often reported in women. Male patients more often presented somatic pain mechanisms. Neuropathic pain was associated with higher mean VAS intensity and was equally reported in male and female patients and in the different age groups. Very old patients, who received less chemotherapy, required less opioid doses and reported a lower intensity of some symptoms, while reporting similar pain relief. Dry mouth was more frequent in adults than in very old patients. The identification of specific factors and pain characteristics may be useful in suggesting the likelihood of response in terms of analgesia and opioid-related adverse effects. Age and gender analysis should be included in all cancer pain and symptom control studies, as they may have an influence on cancer pain prognosis.
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PMID:Factors influencing the opioid response in advanced cancer patients with pain followed at home: the effects of age and gender. 1073 59

Neuropathic pain has been postulated to be mediated, in part, by amino acid neurotransmitters including glycine. The current study examined the effects of continuous intrathecal glycine administration (0.1 mumol 0.5 microliter-1 h-1) on the development of mechanical hyperalgesia and other features of neuropathic pain evoked by unilateral loose ligation of the sciatic nerve in the rat. Each hind paw was tested for withdrawal threshold to mechanical stimuli prior to, and after ligation at intervals of 3, 6, 9, 12 and 16 days. Pain behavior (posture and gait) and hind paw dystrophic features (redness and swelling) were also examined. Glycine increased the normal mechano-nociceptive responses and prevented the development of mechano-nociceptive hyperalgesia. Spontaneous nociceptive behavior and hind paw dystrophic features, seen in the saline treated rats, were significantly diminished. Our results suggest that spinal cord inhibitory glycinergic activity is important for normal mechano-receptive responsitivity and development of mechano-nociceptive hyperalgesia in this model.
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PMID:Long-term intrathecal administration of glycine prevents mechanical hyperalgesia in a rat model of neuropathic pain. 1076 3

Neuropathic pain is often associated with the appearance of pain in regions not related to the injured nerve. One mechanism that may underlie neuropathic pain is abnormal, spontaneous afferent drive which may contribute to NMDA-mediated central sensitization by the actions of glutamate and by the non-opioid actions of spinal dynorphin. In the present study, injuries to lumbar or sacral spinal nerves elicited elevation in spinal dynorphin content which correlated temporally and spatially with signs of neuropathic pain. The increase in spinal dynorphin content was coincident with the onset of tactile allodynia and thermal hyperalgesia. Injury to the lumbar (L(5)/L(6)) spinal nerves produced elevated spinal dynorphin content in the ipsilateral dorsal spinal quadrant at the L(5) and L(6) spinal segments and in the segments immediately adjacent. Lumbar nerve injury elicited ipsilateral tactile allodynia and thermal hyperalgesia of the hindpaw. In contrast, S(2) spinal nerve ligation elicited elevated dynorphin content in sacral spinal segments and bilaterally in the caudal lumbar spinal cord. The behavioral consequences of S(2) spinal nerve ligation were also bilateral, with tactile allodynia and thermal hyperalgesia seen in both hindpaws. Application of lidocaine to the site of S(2) ligation blocked thermal hyperalgesia and tactile allodynia of the hindpaws suggesting that afferent drive was critical to maintenance of the pain state. Spinal injection of antiserum to dynorphin A((1-17)) and of MK-801 both blocked thermal hyperalgesia, but not tactile allodynia, of the hindpaw after S(2) ligation. These data suggest that the elevated spinal dynorphin content consequent to peripheral nerve injury may drive sensitization of the spinal cord, in part through dynorphin acting directly or indirectly on the NMDA receptor complex. Furthermore, extrasegmental increases in spinal dynorphin content may partly underlie the development of extraterritorial neuropathic pain.
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PMID:Extraterritorial neuropathic pain correlates with multisegmental elevation of spinal dynorphin in nerve-injured rats. 1077 75

Deafferentation pain syndromes developing after peripheral nerve lesions are difficult to treat. According to the follow-up (mean: 39.5 months) of 6 patients suffering from causalgic pain we will present our method of augmentative therapy in chronic neuropathic pain caused by peripheral nerve lesions, i.e., peripheral nerve stimulation (PNS), spinal cord stimulation (SCS) and chronic intrathecal opioid infusion. None of the patients showed intraoperative or follow-up complications. Evaluated by visual analogue scales all patients reported a good to excellent pain relief (75-100%). (1) Regarding the favourable long-term results of PNS, this method should be considered in cases of mononeuropathic pain syndromes. (2) Neuropathic pain syndromes which are not assignable to a singular nerve lesion, can often be managed effectively by SCS. (3) In contrast to the widespread opinion, deafferentation pain syndromes of central or peripheral origin can be treated satisfactorily by intrathecal opiate administration.
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PMID:Augmentative treatment of chronic deafferentation pain syndromes after peripheral nerve lesions. 1079 66

Neuropathic pain is highly prevalent in patients with cancer and patients with AIDS, has profound effects on ability to function and quality of life, and is undertreated. Multiple obstacles to the adequate treatment of pain in patients with cancer and AIDS have been identified. Specific factors relevant to neuropathic pain, as well as the prevalence of substance abuse disorders in the AIDS population, contribute heavily to the undertreatment of pain in these patients. The differential diagnosis of neuropathic pain in these settings is broad, and a methodical diagnostic approach is required to achieve the primary objective of effective primary therapy. The parallel objective of providing optimal analgesic treatment also requires an aggressive and systematic approach. The presence of comorbid substance abuse issues requires special considerations that ordinarily do not compromise analgesic approaches. This review summarized the neuropathic pain syndromes seen in cancer and in AIDS, presents principles of pain assessment, highlights treatment options, and addresses the issue of pain and chemical dependency.
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PMID:Neuropathic pain in cancer and AIDS. 1087 Jul 39

Some studies have assessed inflammatory cells such as macrophages, lymphocytes, and neutrophils in herniated lumbar disc tissues using histologic analysis. However, there is no consensus regarding the relationships between clinical symptoms, including radicular pain and the presence of inflammatory cells. It has been shown that autologous nucleus pulposus relocated on the lumbar nerve root in rats produces time dependent and reversible mechanical hyperalgesia, which is thought to be a pain related behavior in peripheral neuropathic pain models. The purpose of this study was to determine whether leukocytes play a role in the mechanical hyperalgesia induced by the nucleus pulposus and to characterize the role of leukocytes in radicular pain attributable to lumbar disc herniation. Nitrogen mustard was used to induce and evaluate leukocytopenia in rats. Sensitivity to mechanical noxious stimuli was measured quantitatively, and inflammatory cells in granulation tissue around the nerve root were examined histologically. The nucleus pulposus produced neither mechanical hyperalgesia nor abundant inflammatory cells in rats with nitrogen mustard induced leukocytopenia. Neuropathic pain produced by the nucleus pulposus, when placed on the nerve root, may be related to inflammatory cell infiltration induced by relocation of the nucleus pulposus, rather than the nucleus pulposus itself.
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PMID:Role of leukocytes in radicular pain secondary to herniated nucleus pulposus. 1090 84

Neuropathic pain is associated with abnormal tactile and thermal responses that may be extraterritorial to the injured nerve. Importantly, tactile allodynia and thermal hyperalgesia may involve separate pathways, since complete and partial spinal cord lesions have blocked allodynia, but not hyperalgesia, after spinal nerve ligation (SNL). Furthermore, lesions of the dorsal column, and lidocaine microinjected into dorsal column nuclei block only tactile allodynia. Conversely, thermal hyperalgesia, but not tactile allodynia was blocked by desensitization of C-fibers with resiniferotoxin. Therefore, it seems that tactile allodynia is likely to be mediated by large diameter A beta fibers, and not susceptible to modulation by spinal opioids, whereas hyperalgesia is mediated by unmyelinated C-fibers, and is sensitive to blockade by spinal opioids. Additionally, abnormal, spontaneous afferent drive in neuropathic pain may contribute to NMDA-mediated central sensitization by glutamate and by non-opioid actions of spinal dynorphin. Correspondingly, SNL elicited elevation in spinal dynorphin content in spinal segments at and adjacent to the zone of entry of the injured nerve along with signs of neuropathic pain. Antiserum to dynorphin A(1-17) or MK-801 given spinally blocked thermal hyperalgesia, but not tactile allodynia, after SNL, and also restored diminished morphine antinociception. Finally, afferent drive may induce descending facilitation from the rostroventromedial medulla (RVM). Blocking afferent drive with bupivicaine also restored lost potency of PAG morphine, as did CCK antagonists in the RVM. This observation is consistent with afferent drive activating descending facilitation from the RVM, and thus diminishing opioid activity, and may underlie the clinical observation of limited responsiveness of neuropathic pain to opioids.
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PMID:Spinal and supraspinal mechanisms of neuropathic pain. 1091 21

Mechanical allodynia- and hyperalgesia-like behavior which develops in rats after L5 spinal nerve lesion has been suggested to be due to ectopic activity in the lesioned afferent neurons originating at the lesion site and/or in the dorsal root ganglion because it is eliminated by section of the dorsal root. Here we reevaluated the effect of a dorsal rhizotomy in rats after L5 spinal nerve lesion. Using calibrated von Frey hairs, paw withdrawal threshold to single stimuli and paw withdrawal incidence to repetitive stimulation were tested before and after nerve section. Neuropathic pain behavior of similar time course and magnitude also developed after cutting the L5 dorsal root, and L5 spinal nerve lesion-induced abnormal behavior could not be reversed by dorsal rhizotomy. The neuropathic pain behavior elicited by dorsal root section also developed when impulse conduction in the dorsal root axons was blocked during rhizotomy by a local anesthetic, i.e. when the immediate injury discharge was prevented from reaching the spinal cord. These results challenge the widely accepted idea that neuropathic pain behavior developing after spinal nerve lesion is dependent on ectopic activity in the lesioned afferent neurons. However, the present results do not rule out the possibility that after the two nerve lesions the mechanisms generating neuropathic pain behavior are different. After dorsal rhizotomy neuropathic pain behavior may be related to deafferentation whereas after spinal nerve lesion it may be caused by ectopic activity.
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PMID:Dorsal root section elicits signs of neuropathic pain rather than reversing them in rats with L5 spinal nerve injury. 1092 14

Neuropathic pain is a disabling feature of peripheral nerve injury. Following injury, local inflammation and the release of mediators may contribute to ectopic mechanosensitivity of the nerve-trunk and pain hypersensitivity. In the present study we investigated whether nitric oxide (NO) action and local nitric oxide synthase (NOS) expression play a role in pain hypersensitivity and A fibre-mediated ectopic hyperexcitability following a chronic constriction injury to a rat sciatic nerve. Using immunohistochemical methods we provide evidence for a unique endothelial constitutive nitric oxide synthase (ecNOS) immunoreactivity localized in early axonal endbulb-like structures of injured peripheral nerve axons. Moreover, we show that following nerve injury there is increased ecNOS-mRNA expression within the lumbar sympathetic ganglia, and that axoplasmic transport in sympathetic and other axons rather than local non-neural synthesis accounts for its accumulation in nerve fibres. We also demonstrate here that local inhibition of NOS action with the broad-spectrum inhibitor NG-nitro-L-arginine-methyl ester (L-NAME), but not more specific inhibitors of other NOS isoforms, has stereospecific, dose- and time-dependent analgesic effects that were reversed by local administration of L-arginine, the natural precursor of NO. In further work, using a teased fibre preparation, we show that administration of L-NAME, but not D-NAME, to the injury site also blocks ectopic mechanosensitivity of injured A-fibres. Our results indicate that an early and transient local ecNOS expression within early axonal endbulb-like structures, some arising from sympathetic axons, plays a critical role in the development of neuropathic pain.
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PMID:Transient action of the endothelial constitutive nitric oxide synthase (ecNOS) mediates the development of thermal hypersensitivity following peripheral nerve injury. 1094 11

Neuropathic pain is difficult to diagnose and treat. Both can be made easier if the nerve dysfunction can be quantified. The two basic modes of evaluation are subjective and objective. This article presents currently used methods in both arenas. Discussion is also given to some basic neurophysiology necessary to understanding the use of these testing methods.
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PMID:Measurement of nerve dysfunction in neuropathic pain. 1099 47


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