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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 syndromes are commonly seen in clinical practice and are frequently used as pain models in testing new therapies. However, no pain scale exists with the primary purpose to measure pain in neuropathic syndromes. This paper describes the development and preliminary validation of the Neuropathic Pain Scale (NPS), which is designed to assess distinct pain qualities associated with neuropathic pain. Results support the discriminant and predictive validity of the NPS items. Moreover, the NPS items appear to be sensitive to treatments known to impact neuropathic pain. These findings provide support for the further development of the NPS.
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PMID:Development and preliminary validation of a pain measure specific to neuropathic pain: the Neuropathic Pain Scale. 904 Jul 16

Cancer pain generally responds in a predictable way to analgesic drugs and drug therapy is the mainstay of treatment. A small proportion of patients, of the order of 20%, have pain that does not respond well to conventional analgesic management. Because opioid analgesics are the most important part of this pharmacological approach, a terminology has developed which centres around whether or not pain will respond to opioid analgesics. The terms opioid-responsive-pain and opioid-non-responsive pain, or opioid-resistant-pain, have been used to differentiate between patients whose pain falls into these two broad groups. This terminology is not satisfactory because it implies an all or none phenomenon, that is that pain either does or does not respond to opioid analgesics. Rarely is there such a clear distinction in practice. This is because the end point when titrating dose against pain with strong opioid analgesics is not simply pain relief or lack of relief: adverse effects may limit dose titration. It is preferable to describe patients with pain which is relatively less sensitive to opioids and/or patients where there is an inbalance between analgesia and unwanted effects as having "opioid-poorly-responsive pain". A pragmatic definition of opioid-poorly-responsive pain is pain that is inadequately relieved by opioid analgesics given in a dose that causes intolerable side effects despite routine measures to control them. Included in this definition is so called paradoxical pain which is not a distinct entity. Neuropathic pain is the most common form of opioid-poorly-responsive pain. The underlying pathophysiology remains unclear but abnormal metabolism of morphine is not the cause of a poor response to this drug. Patients with opioid-poorly-responsive-pain should be considered for treatment with the same opioid by an alternative (spinal) route or with an alternative opioid agonist administered by the same route (whether oral or parenteral), in conjunction with adjuvant analgesics such as tricyclic antidepressants. The most commonly used alternative oral opioids are phenazocine and methadone; transdermal fentanyl is an additional option.
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PMID:Opioid responsiveness. 906 Oct 99

Neuropathic pain states are accompanied by increased sensitivity to both noxious and non-noxious sensory stimuli, characterized as hyperalgesia and allodynia, respectively. In animal models of neuropathic pain, the presence of hyperalgesia and allodynia are accompanied by neuroplastic changes including increased spinal levels of substance P, cholecystokinin (CCK), and dynorphin. N-Methyl-D-aspartate (NMDA) receptors appear to be involved in maintaining the central sensitivity which contributes to neuropathic pain. In addition to its opioid activities, dynorphin has been suggested to act at the NMDA receptor complex. In an attempt to mimic the increased levels of spinal dynorphin seen in animal models of neuropathic pain, rats received a single intrathecal (i.t.) injection of dynorphin A(1-17), dynorphin A(1-13), dynorphin A(2-17) or dynorphin A(2-13) through indwelling catheters. Tactile allodynia was determined by measuring response threshold to probing with von Frey filaments. Dynorphin A(1-17) administration evoked significant and long-lasting tactile allodynia (i.e. > 60 days). Likewise, the i.t. administration of dynorphin A(1-13) or dynorphin A(2-17) or dynorphin A(2-13) also produced long-lasting tactile allodynia. Intrathecal pretreatment, but not post-treatment, with MK-801 prevented dynorphin A(1-17)-induced development of allodynia; i.t. administration of MK-801 alone had no effect on responses to tactile stimuli. In contrast, i.t. pretreatment with naloxone did not affect the development of tactile allodynia induced by dynorphin A(1-17) or alter sensory threshold when given alone. These results demonstrate that a single dose of dynorphin A, or its des-Tyr fragments, produces long-lasting allodynia which may be irreversible in the rat. Further, this effect appears to be mediated through activation of NMDA, rather than opioid, receptors. While the precise mechanisms underlying the development and maintenance of the allodynia is unclear, it seems possible that dynorphin may produce changes in the spinal cord, which may contribute to the development of signs reminiscent of a "neuropathic' state. Given that levels of dynorphin are elevated following nerve injury, it seems reasonable to speculate that dynorphin may have a pathologically relevant role in neuropathic pain states.
Pain 1996 Dec
PMID:Single intrathecal injections of dynorphin A or des-Tyr-dynorphins produce long-lasting allodynia in rats: blockade by MK-801 but not naloxone. 912 15

Neuropathic pain may result from sustained firing of sensory neurones. The questions are what initiates and what stops that firing? Spontaneous firing of a modified Hodgkin-Huxley model axon is induced here by: (1) a depolarizing shift in the K+ channel activation parameter; and (2) a positive change in the K+ equilibrium potential. The duration and pattern of spontaneous discharge is seen to be critically dependent on the level and kinetics of Na+ channel slow inactivation. Slow inactivation of voltage-gated ion channels could be major factors in the induction and treatment of neuropathic pain.
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PMID:Slow Na+ channel inactivation and bursting discharge in a simple model axon: implications for neuropathic pain. 913 79

Until now, there have not been any parameters to monitor opioid therapy in cancer patients with pain. In this study, 325 consecutive advanced cancer patients were scheduled for a prospective longitudinal survey. After exclusions, 67 patients were surveyed. All included patients were advanced cancer patients with pain that required opioid therapy for more than 6 weeks before death. Opioid escalation, symptoms associated with opioid therapy, pain mechanism, and pain intensity were recorded. Indices were calculated to categorize the response to opioids. The opioid escalation index (OEI) was used to index the mean increase of the starting opioid dosage, expressed as a percentage or in mg. The length of the period of stable dose (MLD) and the effective analgesic score (EAS), that is, the analgesic consumption/pain relief ratio calculated at fixed intervals, were also used. Patients with a mean visual analogue scale score (VAS) of less than 4 and regular OEI and EAS were considered responsive; patients with a mean VAS less than 4 but with an OEI more than 5 or increases of more than 100% of EAS when compared to that calculated the week before were considered mildly responsive; and patients with a mean VAS more than 4 were considered unresponsive. Advanced age, female gender, and previous chemotherapy were all factors reducing OEI. Head and neck cancer was associated with a higher OEI. Regarding the influence of the opioid-related symptoms, an increased OEI was associated with the presence of confusion. Moreover the presence of confusion was associated with neuropathic pain. Neuropathic pain taken alone, however, did not influence this score. Gender-specific cancer, such as breast cancer, influenced the gender differences reported for MLD (significantly longer than that reported for males and other primary tumor). Good responsiveness was observed in 28 patients, partial responsiveness in 33 patients, unresponsiveness in six patients. Psychological factors were associated with poor pain relief, probably reducing the patient's compliance. The tools used in this study may be useful in monitoring the effects of opioid therapy in cancer pain patients. Simple numbers are easy to compare and make it possible to profile opioid responsiveness and differences among patients.
J Pain Symptom Manage 1997 Apr
PMID:Monitoring of opioid therapy in advanced cancer pain patients. 913 31

This article has discussed the peripheral and central mechanisms of the various orofacial pain conditions, including musculoskeletal disorders, neurogenic inflammation, and neuropathic pain. To make an accurate diagnosis of orofacial pain and render treatment, all organ systems need to be considered and evaluated. Central sensitization was discussed as it relates to musculoskeletal disorders and neuropathic pain. It has been suggested that treatment of these disorders be problem oriented, addressing both peripheral and central mechanisms if present. Musculoskeletal disorders are characterized by pain that is provokable with function and manipulation. Neurovascular pain is episodic with pain-free periods between attacks. The pain is not related to or provoked by jaw function. Neuropathic pain is more continuous and may be aggravated by light touch. Neuropathy with peripheral involvement responds variably to local anesthetics but may need to be treated with topical or local agents as well as centrally acting agents. Neuropathic pain that does not respond to topical or local agents is more profoundly centralized. These conditions need to be treated with centrally acting agents. In addition, if there is no response to medications, sympathetic involvement needs to be ruled out with sympathetic ganglion blockade.
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PMID:Orofacial pain mechanisms and their clinical application. 914 78

Chronic pain may result from hyperexcitability following activation of spinal NMDA receptors. A naturally-derived mammalian peptide, histogranin, may possess NMDA antagonist activity. This study explored the possibility that stable analog [Ser1]Histogranin (SHG) could reduce chronic pain. Neuropathic pain was induced using the chronic constriction injury model (CCI). Intrathecal injection of SHG markedly attenuated the hyperalgesia and allodynia resulting from CCI, nearly normalizing responses. These results suggest that the natural peptide histogranin may be a novel adjunct in neuropathic pain management.
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PMID:Suppression of neuropathic pain by a naturally-derived peptide with NMDA antagonist activity. 917 1

Neuropathic pain following nerve injury is believed to involve excitatory amino acids (EAAs) and Ca2+-mediated neuronal plastic changes in the central nervous system (CNS). This study was designed to investigate the changes in glutamate and aspartate contents in the dorsal half of the spinal cord following chronic constrictive injury (CCI) of the rat common sciatic nerve. We also examined the changes in intracellular calcium ion concentration ([Ca2+]i) of the spinal dorsal horn in transverse spinal slices in the same animal model. Thermal and mechanical hyperalgesia were observed on day 2 and thereafter following CCI (P < 0.0001). In the CCI rats to which 0.5 mg/kg of i.p. MK-801 was given 30 min prior to CCI and subsequently three daily treatments with 0.5 mg/kg of i.p. MK-801, the development of thermal and mechanical hyperalgesia was suppressed for a period of up to 7 days; however, hyperalgesia appeared on day 10 and day 14 (P < 0.001). In CCI rats, significant increases were observed in glutamate and aspartate contents on the ipsilateral side of the dorsal horn to nerve ligation on days 4, 7 and 14 (P < 0.001). Moreover, significant increases in [Ca2+]i in the spinal dorsal horn were also observed in the superficial (lamina I-II) and deep layers (lamina V-VI) on the ipsilateral side to nerve ligation on days 4, 7 and 14 after nerve ligation in the spinal slices (P < 0.0001). The treatment with i.p. MK-801 suppressed the increases in the contents of glutamate and aspartate and in [Ca2+]i on days 4 and 7. However, the ipsilateral contents of glutamate and aspartate significantly increased on day 14 (P < 0.001 and 0.003, respectively); the increased [Ca2+]i was also observed on day 14 (P < 0.001), and the spatial pattern of the increased regions was similar to untreated CCI rats. We interpret these results to indicate that neuropathic hyperalgesia induced by CCI in the rat is associated with an increase in glutamate and aspartate contents and the subsequent activation of NMDA receptors, followed by an increase in [Ca2+]i within dorsal horn of the spinal cord.
Pain 1996 Nov
PMID:Involvement of increased excitatory amino acids and intracellular Ca2+ concentration in the spinal dorsal horn in an animal model of neuropathic pain. 925 3

Neuropathic pain or persistent dysesthesias may be initiated by mechanical, chemical, or ischemic damage to peripheral sensory nerves. In animal models of neuropathic pain, transection or constrictive injury to peripheral nerves produces ectopic discharges originating at both injury sites and related dorsal root ganglia (DRG), and, consequently, hyperexcitability in associated dorsal horn (DH) neurons of the spinal cord. Since ectopic discharges are inhibited by agents that block voltage-sensitive Na+ channels, it has been postulated that accumulation of Na+ channels in the membrane at nerve injury sites may contribute to, or be responsible for, the development of ectopic neuronal activity (ENA). The present study therefore, tested the sensitivity of ENA to intravenously administered tetrodotoxin (TTX), an extremely potent and selective Na+ channel blocker. Comparative effects of TTX on cardiac parameters such as heart rate (HR) and diastolic blood pressure (DBP) were also studied. Experiments were performed on adult male Sprague-Dawley rats in which the common sciatic nerve had been transected 4-10 days earlier. Neuromal activity was measured in fine bundles of microfilaments teased from sciatic nerves, and extracellular microelectrode recordings were made from DRG and DH neurons. Cardiovascular parameters were recorded simultaneously. Intravenously administered TTX induced dose-dependent inhibition of ENA, with that originating from neuromas being the most sensitive; ED50 values (expressed as microg/kg, with 95% confidence limits) for neuromal, DRG and DH neuron activity were: 0.8 (0.6-1.2), 4.3 (2.2-8.4) and 36.2 (16.1-81.3), respectively. Inhibition of ENA in neuromas and DRG did not recover within 10 min after 100 or 300 microg/kg TTX. By comparison, the ED50 value for the initial decrease of HR was 17.9 (15.0-21.5) microg/kg, and partial recovery occurred within approximately 3 min. These data support the hypothesis that Na+ channel accumulation contributes to the generation of ectopic discharges in neuromas and DRG, and suggest that TTX-sensitive Na+ channels located at the nerve injury site and DRG play an important role in the genesis of neuropathic pain.
Pain 1997 Aug
PMID:Tetrodotoxin inhibits neuropathic ectopic activity in neuromas, dorsal root ganglia and dorsal horn neurons. 927 86

Neuropathic pain can be triggered by non-painful stimuli (e.g., light touch), a sensory abnormality termed allodynia. The acute blockade of spinal glycine receptors with intrathecal strychnine induces a reversible allodynia-like state in the rat. We describe the application of in vivo differential normal pulse voltammetry with carbon fibre micro-electrodes for monitoring the catechol oxidation current (CAOC) of the locus coeruleus (LC) in the strychnine model of allodynia. In addition, we tested the effect of mexiletine, a drug useful in the management of clinical neuropathic pain in this model. Our results show that somatosensory processing in the spinal cord of urethane-anaesthetized rats is radically altered during glycine receptor blockade such that the normally innocuous stimulus of hair deflection causes the marked activation of the LC as determined using in vivo differential normal pulse voltammetry. Mexiletine suppressed the LC and cardiovascular responses of strychnine induced allodynia. Results of this study indicate that LC CAOC, an index of LC neuronal activity: (a) is a sensitive biochemical index of strychnine-allodynia; (b) is temporally correlated with the cardiovascular and motor responses evoked by hair deflection during glycine receptor blockade; and (c) can be used to quantitate allodynia in the strychnine model.
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PMID:Use of differential normal pulse voltammetry for the measurement of locus coeruleus catecholaminergic metabolism in an acute anaesthetized rodent model of allodynia: effect of mexiletine. 933 35


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