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Query: UMLS:C0030193 (pain)
 261,466 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nonopioid and adjuvant analgesics encompass a huge range of heterogenous drugs that differ chemically and mechanistically. These drugs generally are prescribed for mild-to-moderate pain, as coanalgesics for severe pain, or to target specific pain-generating mechanisms. This article provides an overview of some of the more commonly used nonopioid and adjuvant analgesics used to treat chronic pain, including salicylates, acetaminophen, nonsteroidal anti-inflammatory drugs, tricyclic antidepressants, anticonvulsants, N-Methyl-D-Aspartate receptor antagonists, lidocaine, skeletal muscle relaxants, and topical analgesics.
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PMID:Nonopioid and adjuvant analgesics in chronic pain management: strategies for effective use. 1456 2

Ketamine has diverse effects that may be of relevance to chronic pain including: N-methyl-D-aspartic acid, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid, kainate, gamma-aminobutyric acid(A) receptors; inhibition of voltage gated Na(+) and K(+) channels and serotonin, dopamine re-uptake. Ketamine has been in clinical practice for over 30 yr; however, there has been little formal research on the effectiveness of ketamine for chronic pain management. In this review we evaluate the available clinical data as a basis for defining the potential use of ketamine for chronic pain. Literature referenced in this review was obtained from a computer search of EMBASE and MEDLINE from 1966 through August, 2002. Search terms included ketamine, ketalar, pain, painful, analgesic, and analgesia. Abstracts were screened for relevance and publications relating to chronic pain use were obtained. Levels of evidence were stratified according to accepted guidelines (level I-IV). For central pain, there is level II and level IV evidence of efficacy for parenteral and oral ketamine. For complex regional pain syndromes, there is only level IV evidence of efficacy of epidural ketamine. For fibromyalgia, there is level II evidence of pain relief, reduced tenderness at trigger points, and increased endurance. For ischemic pain, a level II study reported a potent dose-dependent analgesic effect, but with a narrow therapeutic window. For nonspecific neuropathic pain, level II and level IV studies reported divergent results with questionable long-term effects on pain. For phantom limb pain and postherpetic neuralgia, level II and level II studies provided objective evidence of reduced hyperpathia and pain relief was usually substantial either after parenteral or oral ketamine. Acute on chronic episodes of severe neuropathic pain represented the most frequent use of ketamine as a "third line analgesic," often by IV or subcutaneous infusion (level IV). In conclusion, the evidence for efficacy of ketamine for treatment of chronic pain is moderate to weak. However, in situations where standard analgesic options have failed ketamine is a reasonable "third line" option. Further controlled studies are needed.
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PMID:Ketamine in chronic pain management: an evidence-based review. 1463 51

The effective treatment of patients suffering from neuropathic cancer pain remains a clinical challenge. When patients experience either insufficient analgesia or problematic side-effects after opioid administration, intrathecal administration of morphine and other medications such as bupivacaine and clonidine may offer significant advantages. Additionally, ketamine, a non-competitive N-methyl-D-Aspartate-receptor antagonist is able to alter pain perception at the spinal level. Because of the potential neurotoxicity after neuraxial use of racemic ketamine, intrathecal administration of the preservative-free active compound, S (+)-ketamine may be a valuable alternative. In this paper, we present a patient with severe neuropathic cancer pain successfully treated by continuous intrathecal infusion of morphine, bupivacaine, clonidine and S (+)-ketamine. Moreover, quality of life measurements before and 3 weeks after the start of spinal treatment revealed an improvement in pain relief and a higher overall quality of life. No clinical signs of neurologic deficit were observed during spinal treatment with S (+)-ketamine. However, the continuous intrathecal administration of S (+)-ketamine should be considered as the last resort because there are no preclinical safety data with relevant concentrations on intrathecal use of S (+)-ketamine.
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PMID:Treatment of neuropathic cancer pain with continuous intrathecal administration of S +-ketamine. 1499 49

The brain-derived interleukin-1beta (IL-1beta) has been involved in the modulation of nociceptive processing. The direction of the effects, however, analgesia or hyperalgesia, is controversial. Here, we report the role of IL-1beta injected intracisternally in orofacial pain transmission. Experiments were carried out on 90 male SD rats and surgical procedures were performed under pentobarbital sodium. Intracisternal injection of 0.3 or 0.6 microg of N-methyl-d-aspartic acid (NMDA) produced intense scratching behavioral responses including vocalization, agitation and a desire to escape in a dose-related manner. The intracisternal injection of 1 or 10 ng IL-1beta significantly decreased the NMDA-evoked scratching behavioral responses. Pretreatment with an IL-1 receptor antagonist or naloxone, an opioid receptor antagonist, blocked the IL-1beta-induced antinociceptive response. These results suggest that cytokine injected intracisternally seems to produce antinociceptive effects in the NMDA-evoked pain model of the orofacial area and the antinociceptive effect seems to be mediated by an opioid pathway.
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PMID:Interleukin-1 beta injected intracisternally inhibited NMDA-evoked behavioral response in the orofacial area of freely moving rats. 1508 73

Injury to peripheral nerves may result in severe and intractable neuropathic pain. Many efforts have been focused on the elucidation of the mechanisms of neuropathic pain. It was found here that integrin plays an important role in the induction of neuropathic pain and treatment of disintegrin is able to attenuate neuropathic pain. The rats were induced hyperalgesia by tightly ligating the L5 spinal nerve and cut just distal to the ligature on one side. Mechanical and thermal stimuli were applied in the middle dermatome of the hind paw. Epidural administration of triflavin (TFV), an arginine-glycine-aspartic acid (RGD) containing disintegrin, inhibited hyperalgesia induced by either mechanical or thermal stimulation. Immunohistochemistry showed that the sprouting of sympathetic nerves into DRG by neuropathic surgery was markedly inhibited by TFV. Beta 1 integrin mRNA of L5 DRG increased immediately 1 day after tight ligation and cut of L5 spinal nerve. However, beta 1 integrin mRNA in uninjured L4 DRG increased later on Day 3 after surgery. On the other hand, alpha-CGRP precursor mRNA decreased in ipsilateral L5 DRG but increased in L4 DRG after neuropathic surgery. Immunohistochemistry shows that beta 3 integrins of L5 as well as L4 increased in response to neuropathic surgery and administration of triflavin antagonized the increasing action. These results suggest that there is interaction between injured and uninjured neurons and the induction of neuropathic pain is related to neuronal sprouting. Disintegrin is able to inhibit neuronal sprouting and the induction of hyperalgesia induced by peripheral nerve injury and may thus be a new category of drugs to be developed for the treatment of neuropathic pain.
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PMID:Inhibition of neuropathic pain by a potent disintegrin--triflavin. 1536 8

Whether preemptive analgesic interventions are more effective than conventional regimens in managing acute postoperative pain remains controversial. We systematically searched for randomized controlled trials that specifically compared preoperative analgesic interventions with similar postoperative analgesic interventions via the same route. The retrieved reports were stratified according to five types of analgesic interventions: epidural analgesia, local anesthetic wound infiltration, systemic N-methyl-d-aspartic acid (NMDA) receptor antagonists, systemic nonsteroidal antiinflammatory drugs (NSAIDs), and systemic opioids. The primary outcome measures analyzed were the pain intensity scores, supplemental analgesic consumption, and time to first analgesic consumption. Sixty-six studies with data from 3261 patients were analyzed. Data were combined by using a fixed-effect model, and the effect size index (ES) used was the standardized mean difference. When the data from all three outcome measures were combined, the ES was most pronounced for preemptive administration of epidural analgesia (ES, 0.38; 95% confidence interval [CI], 0.28-0.47), local anesthetic wound infiltration (ES, 0.29; 95% CI, 0.17-0.40), and NSAID administration (ES, 0.39; 95% CI, 0.27-0.48). Whereas preemptive epidural analgesia resulted in consistent improvements in all three outcome variables, preemptive local anesthetic wound infiltration and NSAID administration improved analgesic consumption and time to first rescue analgesic request, but not postoperative pain scores. The least proof of efficacy was found in the case of systemic NMDA antagonist (ES, 0.09; 95% CI, -0.03 to 0.22) and opioid (ES, -0.10; 95% CI, -0.26 to 0.07) administration, and the results remain equivocal.
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PMID:The efficacy of preemptive analgesia for acute postoperative pain management: a meta-analysis. 1572 65

Supraspinal centres biphasically modulate spinal nociceptive transmission, including descending inhibition and facilitation. Recent studies have revealed that descending facilitatory modulation is a key mechanism underlying induction and maintenance of neuropathic and inflammatory pain. The anterior cingulate cortex (ACC) is not only involved in the transmission of pain sensation but also plays a role in processing pain-related emotion. The ACC also widely connects with relevant regions of the descending modulation system. Here we used electrophysiological and behavioural techniques to study the possible pathways behind the modulation of spinal nociceptive transmission from the ACC. C-fibre-evoked field potentials in the spinal dorsal horn were produced by electrical stimulation of the sciatic nerve at an intensity high enough to excite C fibres, and paw withdrawal latencies (PWLs) to noxious heating were recorded. The results showed that high-frequency tetanic electrical stimulation of the ACC both unilaterally enhanced the C-fibre-evoked field potentials in the spinal dorsal horn and bilaterally shortened PWLs, indicating a facilitation of spinal nociception. A similar effect was observed after microinjection of N-methyl-d-aspartic acid (NMDA; 10 nm, 1 microL) or homocysteic acid (HCA; 0.1 m, 1 microL) into the ACC. When the dorsal reticular nucleus (DRt) was electrolytically lesioned, ACC-induced facilitation of spinal nociception was blocked. These results imply that: (i) activation of the ACC may facilitate spinal nociception; (ii) NMDA receptors in the ACC may be involved in descending facilitation; and (iii) the DRt plays a crucial role in mediating ACC-induced facilitation of spinal nociception.
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PMID:Anterior cingulate cortex contributes to the descending facilitatory modulation of pain via dorsal reticular nucleus. 1617 56

Gabapentin is a novel analgesic whose mechanism of action is not known. We investigated in a postoperative pain model whether adenosine triphosphate (ATP)-sensitive K+ (K(ATP)) channels, N-methyl-d-aspartic acid (NMDA) receptors, and Ca2+ channels are involved in the antiallodynic effect of intrathecal gabapentin. Mechanical allodynia was induced by a paw incision in isoflurane-anesthetized rats. Withdrawal thresholds to von Frey filament stimulation near the incision site were measured before and after incision and after intrathecal drug administration. The antiallodynic effect of gabapentin (100 mug) was not affected by intrathecal pretreatment with antagonists of K(ATP) channels, NMDA receptors or gamma-aminobutyric acid (GABA)(A) receptors. K(ATP) channel openers and GABA(A) receptor agonist, per se, had little effect on the postincision allodynic response. The Ca2+ channel blocker of N-type (omega-conotoxin GVIA, 0.1-3 microg), but not of P/Q-type (omega-agatoxin IVA), L-type (verapamil, diltiazem or nimodipine), or T-type (mibefradil), attenuated the incision-induced allodynia, as did gabapentin. Both the antiallodynic effects of gabapentin and omega-conotoxin GVIA were attenuated by Bay K 8644, an L-type Ca2+ channel activator. These results provide correlative evidence to support the contention that N-type Ca2+ channels, but not K(ATP) channels or NMDA or GABA(A) receptors, might be involved in the antiallodynic effect of intrathecal gabapentin.
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PMID:The antiallodynic action target of intrathecal gabapentin: Ca2+ channels, KATP channels or N-methyl-d-aspartic acid receptors? 1636 27

Sex-related differences in the sensitivity to pain and in the response to analgesics have been reported including higher perceptual responses to experimentally induced pain and the higher prevalence of many pain syndromes in women compared with men. This study examines whether alpha2-adrenoceptor-mediated antinociceptive effects are reduced by estrogen which could account for the sex-related differences in pain perception and modulation. Clonidine, an alpha2-adrenoceptor agonist, has been shown to inhibit noxious stimulus-evoked nociceptive behavior as well as the responses of nociceptive neurons in the medullary dorsal horn. Intracisternal microinjection of clonidine (7 microg/5 microl) through the implanted PE-10 cannulae dorsal to the trigeminal region in male, ovariectomized (OVX), and diestrous (DiE) Sprague-Dawley rats produced a strong antinociceptive effect on N-methyl-D-aspartic acid (NMDA)-induced nociceptive scratching behavior and heat-induced face withdrawal nociceptive tests. However, it failed to produce any inhibition in the estradiol-treated ovariectomized (OVX+E) group regardless of the dose of estradiol (1, 10 or 100 microg/100 microl sesame oil) or in the proestrous (ProE) group. Further, clonidine produced dose-dependent effects in male and OVX groups but not in the OVX+E group on the NMDA-induced nociceptive behavior. Finally, the effect of clonidine was reversed by yohimbine, an alpha2-adrenoceptor antagonist, in male and OVX groups on thermal nociceptive test. These results lead us to conclude that activation of alpha2-adrenoceptors produces sex-specific, estrogen dependent modulation of nociception in the trigeminal region of the rat. A decreased alpha2-adrenoceptor-mediated inhibition could be one of the factors responsible for the higher prevalence of pain syndromes in females.
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PMID:Activation of alpha2-adrenoceptors in the trigeminal region produces sex-specific modulation of nociception in the rat. 1693 8

N-Methyl-d-aspartic acid (NMDA) receptors are known to function in the mediation of pain and have a significant role in the development of hyperalgesia following inflammation. Serine phosphorylation regulation of NMDA receptor function occurs in a variety of conditions. No studies have demonstrated a change in phosphorylation of enteric NMDA receptors following colonic inflammation. We examined the levels of NMDA NR1 phosphorylation in trinitrobenzene sulfonic acid (TNBS) induced colitis in rats and compared it to protein translation and the development of visceral hypersensitivity. We have previously, demonstrated an increase in the C1 cassette of NR1 mRNA expression at 14, 21, and 28 days following TNBS administration. In this study, we examined the NR1 serine phosphorylation at 14 days following TNBS injection. Male Sprague-Dawley rats (200-250 g) were treated with TNBS (20mg per rat) diluted in 50% ethanol (n=3) and vehicle controls of 50% ethanol (n=3). TNBS and vehicle controls were administered with a 24 gauge catheter inserted into the lumen of the rat colon. The animals were sacrificed at 14 days after induction of the colitis and their distal colon was retrieved for two-dimensional (2D) western blot analysis. Serine phosphorylation of the NR1 subunit with C1 cassette appears at 14 days after TNBS injection. In contrast, there was no NR1-C1 expression in the vehicle controls and untreated normal controls. These results suggest a role for colonic-NMDA receptor phosphorylation in the development of neuronal plasticity following colonic inflammation. Phosphorylation of NR1 may partially explain visceral hypersensitivity present during colonic inflammation.
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PMID:Phosphorylation of NMDA NR1 subunits in the myenteric plexus during TNBS induced colitis. 1694 39


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