Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030193 (pain)
 261,466 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In this study, we examined whether several types of non-opioid agents would inhibit the pain-related responses of melanoma-bearing mice. Orthotopic inoculation with melanoma into the hind paw induced marked tactile allodynia and mechanical hyperalgesia. A peroral injection (p.o.) of gabapentin (100-300 mg/kg) inhibited the allodynia and hyperalgesia, without effects on gross behaviors. An intraperitoneal injection (i.p.) of ketamine hydrochloride (30 mg/kg) produced partial inhibition in allodynia and hyperalgesia and prostate posture at 15 min after injection. Diclofenac sodium (10 and 30 mg/kg, i.p), mexiletine hydrochloride (20 mg/kg, i.p.), clonidine hydrochloride (0.1 mg/kg, i.p.) and suramin (100 mg/kg, i.p.) were without effects on allodynia and hyperalgesia. Subcutaneous injections of baclofen (3 mg/kg) and N(G)-nitro-L-arginine methyl ester (100 mg/kg) were also without effects. Repeated administration of gabapentin (150 mg/kg, p.o.) produced constant inhibitions, suggesting no analgesic tolerance. Gabapentin may be useful for the management of cancer pain.
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PMID:Suppression by gabapentin of pain-related mechano-responses in mice given orthotopic tumor inoculation. 1267 42

N-(2-Indanyl)-glycinamide hydrochloride (CHF3381) is a novel low-affinity, noncompetitive N-methyl-d-aspartate receptor antagonist. The current study compared the antinociceptive effects of CHF3381 with those of gabapentin and memantine in in vitro and in vivo models of pain. In isolated rat spinal cord, CHF3381 and memantine, but not gabapentin, produced similar inhibition of the wind-up phenomenon. CHF3381 suppressed the maintenance of carrageenan-induced thermal and mechanical hyperalgesia in the rat with a minimum significantly effective dose (MED) of 30 mg/kg p.o. Memantine produced a partial reversal of both thermal and mechanical hyperalgesia (MED = 10 and 15 mg/kg i.p., respectively). Gabapentin reversed mechanical hyperalgesia (MED = 10 mg/kg s.c.), but did not affect thermal hyperalgesia. In the mouse formalin test, CHF3381 and memantine preferentially inhibited the late phase (MED = 30 and 20 mg/kg i.p., respectively); gabapentin inhibited only the late phase (MED = 30 mg/kg s.c.). Unlike morphine, CHF3381 chronic administration was not accompanied by the development of tolerance in the formalin test. Furthermore, morphine tolerance did not cross-generalize to CHF3381. In rats with a sciatic nerve injury, CHF3381 relieved both cold and mechanical allodynia (MED = 100 mg/kg p.o.). In contrast, memantine was inactive. Gabapentin blocked cold allodynia (MED = 30 mg/kg s.c.), but had marginal effects on mechanical allodynia. In diabetic neuropathy, CHF3381 reversed mechanical hyperalgesia (MED = 50 mg/kg p.o.). Memantine (15 mg/kg i.p.) produced an antinociceptive effect, whereas gabapentin (100 mg/kg p.o.) had no significant effect. Thus, CHF3381 may be useful for the therapy of peripheral painful neuropathies.
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PMID:Antinociceptive activity of the N-methyl-D-aspartate receptor antagonist N-(2-Indanyl)-glycinamide hydrochloride (CHF3381) in experimental models of inflammatory and neuropathic pain. 1275 Apr 40

Gabapentin was approved for use in the USA in 1994 as an add-on drug in adults who have partial seizures either alone or with secondary generalised seizures. Its use has been expanded to include treatment for other conditions such as neuropathic pain and paraesthesiae. Gabapentin was prescribed for our patient who had persistent left-sided hemi-paraesthesiae consequential of a previous thalamic infarct. One week after commencement of gabapentin, she developed an adverse reaction in the form of a purpuric rash over bilateral lower limbs. Skin biopsy revealed histological features of cutaneous leukocytoclastic vasculitis. This rash completely resolved with withdrawal of gabapentin and steroidal treatment. This cutaneous adverse reaction to gabapentin has not been reported in the medical literature.
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PMID:A case of cutaneous leukocytoclastic vasculitis associated with gabapentin. 1276 64

Gabapentin was originally designed as an anti-convulsant gamma-aminobutyric acid (GABA) mimetic capable of crossing the blood-brain barrier. In the present review we show that although gabapentin is not a GABA mimetic, it has great utility as an add-on therapy for epilepsy and as a first-line treatment for neuropathic pain. We summarise the studies that have been performed which demonstrate that gabapentin appears to interact with a novel binding site expressed at high density within the central nervous system (CNS), namely the alpha2delta voltage-dependent calcium channel subunit. The review continues by examining the effects of gabapentin on calcium channel function and neurotransmitter release before, in the latter part of the review, summarising the more recently discovered actions of gabapentin in relation to intracellular signalling.
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PMID:Cellular and molecular action of the putative GABA-mimetic, gabapentin. 1278 20

The anticonvulsant drug gabapentin has been demonstrated to alleviate symptoms of painful diabetic neuropathy as well as other types of neuropathic pain. The aim of the present study was to investigate the effect of gabapentin in a recently developed mouse model of peripheral neuropathy. This model is based on a photochemical ischemic lesion of the sciatic nerve generated by laser-induced activation of the photosensitizing dye erythrosin B. Following laser irradiation of the sciatic nerve for 2, 5, or 10 min, tactile allodynia was observed during at least 3 weeks. The degree of allodynia was most marked following 10 min of irradiation. Subcutaneous administration of gabapentin [175-300 micromol/kg ( approximately 30-51 mg/kg), cumulative doses, at 1-h intervals] significantly reversed tactile allodynia induced by 10-min laser irradiation. The maximal dose of gabapentin increased the withdrawal threshold from approximately 0.55 to approximately 1.85 g (i.e., about 77% of the threshold in normal animals, approximately 2.4 g). Gabapentin did not affect the tactile withdrawal threshold in intact animals. A dose of gabapentin (100 micromol/kg, sc) that had no effect on allodynia was found to significantly reduce the pain behavior during phase 2 of the formalin test. The present study demonstrates that systemic administration of gabapentin suppresses both allodynia induced by an ischemic lesion of the sciatic nerve and pain behavior in the formalin test.
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PMID:Gabapentin reverses mechanical allodynia induced by sciatic nerve ischemia and formalin-induced nociception in mice. 1289 53

Central cord syndrome may be associated with severe pain, resistant to conventional pain therapy regimens. Chronic pain may be a persistent problem in rehabilitation of spinal cord injuries. These pain syndromes are long lasting and challenging to treat. Gabapentin has been shown to be useful in treatment of different conditions which may be caused by increased neuronal excitability. This report describes a case where central cord syndrome and its chronic neuropathic pain associated with allodynia was successfully treated with gabapentin.
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PMID:Treatment of chronic neuropathic pain after traumatic central cervical cord lesion with gabapentin. 1292 35

Gabapentin and pregabalin are amino acid derivatives of gamma-amino butyric acid that have anticonvulsant, analgesic, and anxiolytic-like properties in animal models. The mechanisms of these effects, however, are not well understood. To ascertain whether these drugs have effects on sensory neurons, we studied their actions on capsaicin-evoked release of the sensory neuropeptides, substance P and calcitonin gene-related peptide from rat spinal cord slices in vitro. Although release of immunoreactive peptides from non-inflamed animals was not altered by either drug, prior in vivo treatment by intraplantar injection of complete Freund's adjuvant enhanced release from spinal tissues in vitro, which was attenuated by gabapentin and pregabalin. These drugs also reduced release of immunoreactive neuropeptides in spinal tissues pretreated in vitro with the protein kinase C activator, phorbol 12,13-dibutyrate. Our results suggest that gabapentin and pregabalin modulate the release of sensory neuropeptides, but only under conditions corresponding to significant inflammation-induced sensitization of the spinal cord.
Pain 2003 Sep
PMID:Pregabalin and gabapentin reduce release of substance P and CGRP from rat spinal tissues only after inflammation or activation of protein kinase C. 1449 29

Anti-epileptic drugs (AEDs) are increasingly used for the treatment of neuropathic pain. Oxcarbazepine is a recently introduced AED that is effective in treating epilepsy and has an improved side-effect profile compared to existing therapies. Here we have examined the effect of oxcarbazepine and other AEDs in a model of neuropathic pain in the rat and guinea-pig. Oxcarbazepine and carbamazepine (3-100 mg x kg(-1)) did not affect mechanical hyperalgesia or tactile allodynia induced by partial sciatic nerve ligation in the rat following oral administration. However, in the same model in the guinea-pig, both drugs produced up to 90% reversal of mechanical hyperalgesia with respective D(50) values of 10.7 and 0.8 mg x kg(-1). The active human metabolite of oxcarbazepine, monohydroxy derivative, was similarly active against mechanical hyperalgesia in the guinea-pig but not the rat. Lamotrigine (3-100 mg x kg(-1), p.o.) was effective against mechanical hyperlagesia in both species although it showed greater efficacy and potency in the guinea-pig (D(50) 4.7 mg x kg(-1)) compared to the rat (D(50) 27 mg kg(-1)). Lamotrigine produced slight inhibition of tactile allodynia in the rat only at the highest dose tested of 100 mg x kg(-1). Gabapentin was poorly active against mechanical hyperalgesia in both the rat and guinea-pig following a single oral administration (100 mg x kg(-1)), although upon repeated administration it produced up to 70 and 90% reversal in rat and guinea-pig, respectively. Gabapentin did however produce significant dose-related reversal of tactile allodynia in the rat following a single administration. These data show that oxcarbazepine and other AEDs are effective anti-hyperalgesic or anti-allodynic agents in an animal model of neuropathic pain, and provide further support for their use in the treatment of neuropathic pain in the clinic.
Pain 2003 Sep
PMID:Comparative activity of the anti-convulsants oxcarbazepine, carbamazepine, lamotrigine and gabapentin in a model of neuropathic pain in the rat and guinea-pig. 1449 54

Gabapentin is a structural analogue of the neurotransmitter gamma-aminobutyric acid (GABA) approved for use in adults with postherpetic neuralgia. Gabapentin does not bind to GABA(A) or GABA(B) receptors. Its mechanism of action in humans is unclear, but may involve binding to alpha2delta calcium channel subunits in animal models. Reductions in the mean daily pain score from baseline to week 7 or 8 of treatment (primary endpoint) were significantly greater with gabapentin 1800-3600 mg/day than placebo therapy in two well designed trials in patients with postherpetic neuralgia. The proportion of responders (patients showing a > or =50% reduction in mean daily pain score at endpoint versus baseline) was significantly greater with gabapentin than placebo. Daily sleep rating scores, the Short Form McGill Pain Questionnaire (total pain scores), Patient and Clinician Global Impression of Change and measures on the Short Form-36 Health Survey (including physical functioning, role-physical, bodily pain, vitality or mental health) improved to a significantly greater extent with gabapentin than placebo. Adverse events associated with gabapentin in patients with postherpetic neuralgia were usually mild to moderate in intensity, with dizziness, somnolence and peripheral oedema being commonly reported.
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PMID:Gabapentin: in postherpetic neuralgia. 1453 49

Diabetes mellitus is a major health concern that is only expected to become more prevalent over the next few decades. It causes much morbidity and mortality through various macro- and microvascular complications, including diabetic neuropathy. Currently, there is no treatment that directly affects the natural course of diabetic neuropathy except for rigorous glycemic control, a goal that is not always achievable. Despite these therapeutic limitations, the morbidity caused by diabetic neuropathy can be minimized by early and accurate diagnosis. A detailed history and physical examination, along with carefully selected laboratory tests will confirm the presence of diabetic neuropathy while excluding other etiologies that may require alternative management strategies. Treatment is always tailored to the patient's symptoms. In addition to improved glycemic control, health care providers can provide education, support, and symptomatic relief. There are many pain modulating therapies that are effective in diabetic neuropathy as discussed above. Nortriptyline at low doses is an inexpensive well-tolerated medication that is effective. Gabapentin is an excellent choice when nortriptyline is ineffective or not tolerated. Other anticonvulsants, such as lamotrigine, carbamazepine, oxycarbazepine, and topiramate, may also provide benefit. Judicious use of narcotics is appropriate when other treatment modalities fail. The importance of treating underlying depression cannot be overemphasized. When gait becomes impaired as a result of neuropathy, appropriate prescription of assistive devices will prevent injuries from falls. Ankle-foot orthoses and other orthotic devices may allow patients to remain ambulatory and independent for a longer period. Despite the challenges ahead, the future holds the promise of more effective treatments for diabetes mellitus and its complications.
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PMID:Medical evaluation and treatment of diabetic peripheral neuropathy. 1463 32


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