Central Dysesthesia Pain after Traumatic Spinal Cord Injury Is Dependent on N-Methyl-D-aspartate Receptor Activation

Eide, Per Kristian; Stubhaug, Audun; Stenehjem, Aud

doi:10.1227/00006123-199512000-00007

Cited by 208 publications

(68 citation statements)

References 32 publications

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“…54 There was strong evidence that intravenous ketamine is effective in the treatment of post-SCI central or neuropathic pain. 55,56 Ketamine has been shown to be especially effective in treating wind-up pain, which may be due to the fact that temporal summation of pain (windup pain) is mediated by NMDA receptors. Eide et al 57 provided strong evidence that central pain after SCI is dependent on the activation of NMDA receptors.…”

Section: Discussionmentioning

confidence: 99%

“…Wind-up pain is produced by repeated stimulation of c-nociceptive afferents resulting in temporal summation of pain perception. 56 There was a high correlation between the serum concentration of ketamine and the degree of reduction in continuous and wind-up pain.…”

Section: Analgesics For Sci Painmentioning

confidence: 97%

“…In one RCT of 10 subjects, Kvarnstrom et al 55 found ketamine was successful in reducing spontaneous neuropathic pain post SCI. Eide et al 56 in another small RCT (n=9), compared intravenous ketamine hydrochloride (an NMDA receptor antagonist), alfentanil (a μ-opioid receptor agonist) and placebo as either a combination bolus or continuous intravenous infusion. The bolus dose was administered for 60 seconds and the continuous intravenous infusion was started simultaneously for 17-21 minutes during testing.…”

Section: Analgesics For Sci Painmentioning

confidence: 99%

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A Systematic Review of Pharmacologic Treatments of Pain After Spinal Cord Injury

Teasell

Mehta

Aubut

et al. 2010

Archives of Physical Medicine and Rehabilitation

155

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Objective-To conduct a systematic review of published research on the pharmacological treatment of pain after spinal cord injury (SCI).Data Sources-Medline, CINAHL, EMBASE and PsycINFO databases were searched for articles published 1980 to June 2009 addressing the treatment of pain post SCI. Randomized controlled trials (RCTs) were assessed for methodological quality using the PEDro assessment scale, while non-RCTs were assessed using the Downs and Black evaluation tool. A level of evidence was assigned to each intervention using a modified Sackett scale.Study Selection-The review included randomized controlled trials and non-randomized controlled trials which included prospective controlled trials, cohort, case series, case-control, prepost and post studies. Case studies were included only when there were no other studies found.Data Extraction-Data extracted included the PEDro or Downs and Black score, the type of study, a brief summary of intervention outcomes, type of pain, type of pain scale and the study findings.. Data Synthesis-Articles selected for this particular review evaluated different interventions in the pharmacological management of pain post SCI. 28 studies met inclusion criteria: there were 21 randomized controlled trials of these 19 had Level 1 evidence. Treatments were divided into five Conclusions-Most studies did not specify participants' types of pain; hence making it difficult to identify the type of pain being targeted by the treatment. Anticonvulsant and analgesic drugs had the highest levels of evidence and were the drugs most often studied. Gabapentin and pregabalin had strong evidence (five Level 1 RCTs) for effectiveness in treating post-SCI neuropathic pain, as did intravenous analgesics (lidocaine, ketamine and morphine) but the latter only had short term benefits. Tricyclic antidepressants only showed benefit for neuropathic pain in depressed individuals. Intrathecal baclofen reduced musculoskeletal pain associated with spasticity; however there was conflicting evidence for the reduction in neuropathic pain. Studies assessing the effectiveness of opioids were limited and revealed only small benefits. Cannabinoids showed conflicting evidence in improving spasticity related pain. Clonidine and morphine, when given together, had a significant synergistic neuropathic pain-relieving effect.

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Section: Discussionmentioning

confidence: 99%

Section: Analgesics For Sci Painmentioning

confidence: 97%

Section: Analgesics For Sci Painmentioning

confidence: 99%

See 1 more Smart Citation

A Systematic Review of Pharmacologic Treatments of Pain After Spinal Cord Injury

Teasell

Mehta

Aubut

et al. 2010

Archives of Physical Medicine and Rehabilitation

155

View full text Add to dashboard Cite

show abstract

“…67 In nine patients with central neuropathic pain after traumatic SCI, the severity of continuous and evoked pain was examined before and after the intravenous infusion of either the NMDA receptor antagonist ketamine, the mopioid receptor agonist alfentanil or placebo. A randomised, double-blind, cross-over study design was used.…”

Section: Studies In Humansmentioning

confidence: 99%

Pathophysiological mechanisms of central neuropathic pain after spinal cord injury

Eide¹

1998

Spinal Cord

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After spinal cord injury (SCI), between 10% and 20% of the patients may develop central neuropathic pain. This type of chronic pain usually is a very bothersome sequel and represents a major therapeutic challenge since conventional medical and surgical pain therapies generally are ine ective. This review focuses on recent advances in the understanding of the pathophysiology of this pain syndrome. Important clinical features of central neuropathic pain after SCI include loss of sensations mediated by spinothalamic pathways combined with development of abnormal pain perception (spontaneous continuous pain and abnormally evoked pain). Up-regulation of neuronal activity leading to spontaneous and evoked neuronal hyperactivity/hyperexcitability, may be the neurophysiological substrate for development of abnormal pain perception. This paper describes some neurochemical changes that may be important for the induction and maintenance of neuronal hyperactivity and abnormal pain perception: Increased excitatory glutaminergic activity involving N-methyl-D-aspartate (NMDA) receptor activation, may trigger the intracellular cascade reaction leading to upregulation of neuronal activity/excitability. Changes in voltage-sensitive Na + channels may contribute to changes in nerve membrane excitability. Other important mechanisms may be loss of endogenous inhibition, including reduced g-amino-butyric acid (GABA)ergic, opioid and monoaminergic inhibition. These various mechanisms may provide new targets for treatment of a pain syndrome that traditionally has been so di cult to handle.

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“…As increased excitability of spinal dorsal horn neurons has been observed in animal studies following SCI, several underlying mechanisms of SCIinduced pain have been proposed. These include removal of inhibitory influences involving gamma-amino butyric acid (GABA), serotonin, and opioids [3][4][5][6], an increase in glutamatergic excitatory effects via activation of N-methyl-Daspartate (NMDA) and non-NMDA receptors [7][8][9], and anatomical reorganization in the spinal cord with sprouting of central terminals of primary afferent neurons [10,11].…”

Section: Introductionmentioning

confidence: 99%

Transplantation of GABAergic Neurons from ESCs Attenuates Tactile Hypersensitivity Following Spinal Cord Injury

et al. 2010

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We investigated the therapeutic potential of mouse ESCderived gamma-amino butyric acid (GABA)ergic neurons ($74% of total neurons in vitro) to reduce neuropathic pain following spinal cord injury (SCI) in rats. Spinal cord hemisection at the T13 segment, which is used as a rat SCI pain model, induced tactile hypersensitivity of the hind paw, as evidenced by decreased paw withdrawal thresholds in response to von Frey filaments, and also induced hyperexcitability of wide dynamic range neurons in the lumbar spinal cord in response to natural cutaneous stimuli. At 2 weeks posthemisection, GABAergic neurons (500,000 cells) were transplanted into the subarachnoid space of the spinal lumbar enlargement via a modified lumbar puncture technique. The transplantation of GABAergic neurons led to long-term attenuation of hemisection-induced tactile hypersensitivity and neuronal hyperexcitability as compared with vehicle-treated controls. These attenuations were reversed by the application of bicuculline and CGP52432, GABA-A and GABA-B receptor antagonists, respectively, but not by application of the serotonergic receptor antagonist methylsergide, indicating a specific restoration of spinal GABAergic inhibition. Histological data from sections of the lumbar cord in grafts demonstrated that 43.5% of surviving engrafted cells were neurons and located densely in the lower-medial portion of the dorsal funiculi in the spinal white matter. Among the observed neurons, 26.2% were GABAergic. The results suggest that subarachnoid transplantation of ESC-derived GABAergic neurons appear to restore spinal GABAergic inhibitory tone and can be a promising strategy to treat SCI-induced pain.

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Central Dysesthesia Pain after Traumatic Spinal Cord Injury Is Dependent on N-Methyl-D-aspartate Receptor Activation

Cited by 208 publications

References 32 publications

A Systematic Review of Pharmacologic Treatments of Pain After Spinal Cord Injury

A Systematic Review of Pharmacologic Treatments of Pain After Spinal Cord Injury

Pathophysiological mechanisms of central neuropathic pain after spinal cord injury

Transplantation of GABAergic Neurons from ESCs Attenuates Tactile Hypersensitivity Following Spinal Cord Injury

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