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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 remains a major complication of various forms of injury to peripheral nerves in humans. Recently, 2 models of peripheral mononeuropathy in the rat have been described which closely resemble the human condition. Bennett and Xie3 described one model induced by the placement of 4 loose ligatures around the entire sciatic nerve; Seltzer et al. have described a second model produced by the placement of a tight ligature around one-third to one-half of the sciatic nerve. It is the purpose of this work to compare the effect of these injuries on the time course and magnitude of hyperalgesia as measured by paw withdrawal latency to a radiant heat stimulus. In addition, to evaluate the hypothesis that neuropathic pain develops as a result of injury-associated discharges, some injuries were induced following anesthesia of the sciatic nerve. Our results show that the partial constriction neuropathy (PCN) described by Bennett and Xie3 develops in a faster time frame than that produced by the tight ligature, or partial transection neuropathy (PTN), described by Seltzer and co-workers. In addition, the PCN shows a reduction in both the duration and magnitude of behavioral hyperalgesia obtained for those animals in which local anesthetic (lidocaine) was applied to the sciatic nerve, while the PTN does not show this sensitivity. The data suggest that injury-related discharge is one important factor contributing to the generation of hyperalgesia in the PCN model. The mechanism(s) responsible for the generation of hyperalgesia in the early stages of the PTN model are not lidocaine-sensitive.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Differential influence of local anesthetic upon two models of experimentally induced peripheral mononeuropathy in the rat. 131 90

This series of studies has investigated the involvement of the NMDA receptor and the translocation of PKC in the seemingly unrelated phenomena of neuropathic pain and tolerance and dependence to narcotic analgesic drugs. This work has demonstrated that the NMDA receptor and PKC translocation are importantly involved in neuropathic pain and morphine tolerance or dependence and that these phenomena may be importantly interrelated. Neuropathic pain following nerve injury is a major chronic pain syndrome. Utilizing a rat model of painful peripheral mononeuropathy produced by CCI of the sciatic nerve, the authors have investigated central mechanisms of postinjury neuropathic pain. Behavioral and pharmacological studies indicate that thermal hyperalgesia and spontaneous pain behaviors observed in this model are attenuated by treatment with NMDA receptor antagonists. A consequence of NMDA receptor activation is calcium influx, which in turn can result in translocation of PKC from cytosol to membrane. Inhibitors of intracellular PKC translocation and activation block thermal hyperalgesia and spontaneous pain behaviors after CCI and also reduce the elevated spinal cord neural activity in CCI rats. Furthermore, spinal cord levels of membrane-bound PKC reliably increase in CCI rats as a result of translocation of PKC revealed by the [3H]PDBu autoradiographic assay. This increase in membrane-bound PKC is associated with postinjury neuropathic pain behaviors in CCI rats and both pain-related behaviors and membrane-bound PKC are reduced potently by GM1 ganglioside.
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PMID:The association of neuropathic pain, morphine tolerance and dependence, and the translocation of protein kinase C. 874 91

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

Neuropathic pain affects many patients, and treatment today is far from being perfect. Nav1.8 Na(+) channels, which are expressed by small fibre sensory neurons, are promising targets for novel analgesics. Na(+) channel blockers used today, however, show only limited selectivity for this channel subtype, and can cause dose-limiting side effects. Recently, the secretolytic ambroxol was found to preferentially inhibit Nav1.8 channels. We used this compound as a tool to investigate whether a Nav1.8-preferring blocker can suppress symptoms of chronic, neuropathic and inflammatory pain in animal models. The drug was tested in the formalin paw model, two models of mononeuropathy, and a model of monoarthritis in rats. Ambroxol's effects were compared with those of gabapentin. Ambroxol at a dose of 1g/kg had to be administered to rats to achieve the plasma levels that are reached in clinical use (for the treatment of infant and acute respiratory distress syndrome). Ambroxol (1g/kg) was only weakly effective in models for acute pain, but effectively reduced pain symptoms in all other models; in some cases it completely reversed pain behaviour. In most cases the effects were more pronounced than those of gabapentin (at 100mg/kg). These data show that a Nav1.8-preferring Na(+) channel blocker can effectively suppress pain symptoms in a variety of models for chronic, neuropathic and inflammatory pain at plasma levels, which can be achieved in the clinic.
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PMID:Ambroxol, a Nav1.8-preferring Na(+) channel blocker, effectively suppresses pain symptoms in animal models of chronic, neuropathic and inflammatory pain. 1618 23

Neuropathic pain is result of damage or dysfunction of periphery or central nervous system. There is no adequate adaptation and produce suffering without biological helpfulness. The aim of treatment of patient with neuropathic pain is soothing of pain and suffering and prevention of further development of pathological process. Periphery mechanisms of neuropathic pain include hyperexcitability of cell membrane and periphery sensibilization. Central mechanism includes central sensibilization, central reorganization of alphabeta fibers and loss of inhibition mechanisms. The main symptoms of neuropathic pain are described as lancinating, stabbing, or shooting pain. Hyperalgesia and allodynia are special kind of neuropathic pain that is provoked by mechanic or thermal stimuli. Mononeuropathy, plexopathy, radiculopathy, and myelopathy, lesions of thymus, cortex or brain stem are real cause of neuropathic pain. In the treatment of neuropathic pain drug such as opioid, nonsteroid antirheumatics, analgetics, tricyclic antidepressant and antiepileptic are used. The most successful treatment is with antiepileptic drugs of second generation. Carbamazepin was the drug of choice till ten years ago. Since then the leader position in treatment has belong to gabapentin in dose from 900-2400 mg daily. Currently the new drug is tested, antiepileptic pregabaline. The first experiences are promising.
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PMID:[Neuropathic pain]. 1762 48

Neuropathic pain consequent to peripheral injury is associated with local inflammation and overexpression of nitric oxide synthases (NOS) and inflammatory cytokines in locally recruited macrophages, Schwann and glial cells. We investigated the time course and localization of nitric oxide synthases (NOS) and cytokines in the central (spinal cord and thalamus) and peripheral nervous system (nerve and dorsal root ganglia), in a mouse model of mononeuropathy induced by sciatic nerve chronic constriction injury. ATP is recognized as an endogenous pain mediator. Therefore we also evaluated the role of purinergic signalling in pain hypersensitivity employing the P2 receptor antagonist, pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (PPADS), on pain behaviour, NOS and cytokines. The PPADS daily administration starting on day 3 after injury dose- and time-dependently decreased both tactile allodynia and thermal hyperalgesia. PPADS (25mg/kg) completely reversed nociceptive hypersensitivity and simultaneously reduced the increased NO/NOS system and IL-1beta in both peripheral (injured sciatic nerve and L4-L6 ipsilateral dorsal root ganglia) and central steps of nervous system (L4-L6 spinal cord and thalamus) involved in pain signalling. IL-6 was overexpressed only in the peripheral nervous system and PPADS prolonged administration reduced it in sciatic nerve. In conclusion, we hypothesize that NO/NOS and IL-1beta have a pronociceptive role in this neuropathy model, and that purinergic antagonism reduces pain hypersensitivity by inhibiting their overactivity.
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PMID:The purinergic antagonist PPADS reduces pain related behaviours and interleukin-1 beta, interleukin-6, iNOS and nNOS overproduction in central and peripheral nervous system after peripheral neuropathy in mice. 1790 Aug 7

Incidence rate estimates of neuropathic pain are scanty and mostly address single types whereas the scope of the disease is wide. We aimed to calculate the incidence rates of neuropathic pain conditions in the Dutch general population and to assess treatment strategies in primary care. The study population included persons registered for at least one year in the Integrated Primary Care Information (IPCI) database between 1996 and 2003. Neuropathic pain was ascertained and classified by systematic review of computerized longitudinal medical records. Incidence rates (IR) were calculated, and the treatment for pain was compared to age and gender matched controls. Among 362,693 persons contributing 1,116,215 person years (PY), we identified 9135 new cases of neuropathic pain (IR: 8.2/1000 PY, 95%CI: 8.0-8.4). Mononeuropathy and carpal tunnel syndrome were the most frequent types with 4.3 and 2.3 cases/1000 PY followed by diabetic peripheral neuropathy and post-herpetic neuralgia at 0.72 and 0.42/1000 PY. Neuropathic pain was 63% more common in women than in men and peaked between the ages 70 and 79. More than 50% of cases received pain medication within 6 months after diagnosis, mostly consisting of NSAIDs or aspirin. Anticonvulsants and tricyclic antidepressants were only used by 4.8 and 4.7% of cases. Neuropathic pain is a rather frequent condition with an annual incidence of almost 1% of the general population and affecting women and middle-aged persons more often. The treatment mostly consisted of regular analgesics suggesting that pharmacological treatment of neuropathic pain is suboptimal.
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PMID:Incidence rates and treatment of neuropathic pain conditions in the general population. 1848 97

Peripheral neuropathies are a heterogeneous group of diseases affecting peripheral nerves. The causes are multiple: hereditary, metabolic, infectious, inflammatory, toxic, traumatic. The temporal profile includes acute, subacute and chronic conditions. The majority of peripheral neuropathies cause mainly muscle weakness and sensory loss, positive sensory symptoms and sometimes pain. When pain is present, however, it is usually extremely intense and among the most disabling symptoms for the patients. In addition, the neurological origin of the pain is often missed and patients receive inadequate or delayed specific treatment. Independently of the disease causing the peripheral nerve injury, pain originating from axonal pathology or ganglionopathy privileges neuropathies affecting smaller fibres, a clinical observation that points towards abnormal activity within nociceptive afferents as a main generator of pain. Natural activation of blood vessels or perineurial nociceptive network by pathology also causes intense pain. Pain of this kind, i.e. nerve trunk pain, is among the heralding symptoms of inflammatory or ischemic mononeuropathy and for its intensity represents itself a medical emergency. Neuropathic pain quality rekindles the psychophysical experience of peripheral nerves intraneural microstimulation i.e. a combination of large and small fibres sensation temporally distorted compared to physiological perception evoked by natural stimuli. Pins and needles, burning, cramping mixed with numbness, and tingling are the wording most used by patients. Nociceptive pain instead is most often described as aching, deep and dull. Good command of peripheral nerve anatomy and pathophysiology allows timely recognition of the different pain components and targeted treatment, selected according to intensity, type and temporal profile of the pain.
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PMID:Painful peripheral neuropathies. 1861 40

Neuropathic pain is often accompanied by stress, anxiety and depression. Although there is evidence for involvement of corticotropin-releasing factor (CRF), the detailed neuronal basis of these pain-related mood alterations is unknown. This study shows that peripheral mononeuropathy was accompanied by changes in limbic forebrain CRF, but did not lead to changes in the functioning of the hypothalamo-pituitary-adrenal axis and the midbrain Edinger-Westphal centrally projecting (EWcp) neuron population, which play main roles in the organism's response to acute pain. Twenty-four days after chronic constriction injury (CCI) of the rat sciatic nerve, the oval bed nucleus of the stria terminalis (BSTov) contained substantially more Crf mRNA as did the central amygdala (CeA), which, in addition, possessed more CRF. In contrast, Crf mRNA and CRF contents of the hypothalamic paraventricular nucleus (PVN) were unaffected by CCI. Similarly, EWcp neurons, producing the CRF family member urocortin 1 (Ucn1) and constitutively activated by various stressors including acute pain, did not show an effect of CCI on Ucn1 mRNA or Ucn1. Also, the immediate early gene products cFos and deltaFosB in the EWcp were unaffected by CCI. These results indicate that neuropathic pain does not act via the HPA-axis or the EWcp, but includes a main role of Crf in the limbic system, which is in clear contrast to stressors like acute and chronic pain, which primarily act on the PVN and the EWcp.
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PMID:Experimental neuropathy increases limbic forebrain CRF. 2168 87

Pain may affect all aspects of social life and reduce the quality of life. Neuropathic pain (NP) is common in patients affected by plexopathy, radiculopathy, mononeuropathy, peripheral neuropathy. Phantom limb pain (PLP) is a painful sensation that is common after amputation, and its pathophysiological mechanisms involve changes in the peripheral and central nervous system. Given the lack of conclusive evidence and specific guidelines on these topics, the aim of the Italian Consensus Conference on Pain on Neurorehabilitation (ICCPN) was to collect evidence and offer recommendations to answer currently open questions on the assessment and treatment of NP associated with the above conditions and PLP. When no evidence was available, recommendations were based on consensus between expert opinions. Current guidelines on the assessment and pharmacological treatment of NP can be applied to plexopathy, radiculopathy, mononeuropathy, peripheral neuropathy, while evidence for invasive treatments and physical therapy is generally poor because of the low quality of studies. Treatment of PLP is still unsatisfactory. Data on the functional outcome and impact of pain on neurorehabilitation outcome in these conditions are lacking. In most cases, a multidisciplinary approach is recommended to offer a better outcome and reduce side effects. High quality studies are requested to address the unmet needs in this field.
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PMID:Diagnosis and treatment of pain in plexopathy, radiculopathy, peripheral neuropathy and phantom limb pain. Evidence and recommendations from the Italian Consensus Conference on Pain on Neurorehabilitation. 2783 72


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