The antiepileptic agent gabapentin (Neurontin) possesses anxiolytic-like and antinociceptive actions that are reversed byd-serine

Singh, Lakhbir; Field, Mark; Ferris, Pushpinder; Hunter, John C.; Oles, Ryszard J.; Williams, Richard G.; Woodruff, G.N.

doi:10.1007/bf02805968

Cited by 221 publications

(115 citation statements)

References 27 publications

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“…The antiallodynic effect of pregabalin is consistent with other pharmacological studies performed in somatic pain. Singh et al (1996) demonstrated that systemic administration of pregabalin and gabapentin reduced thermal hyperalgesia after carrageenan-induced inflammation of the paw. In neuropathic pain models, gabapentin blocked the mechanical allodynia in rats.…”

Section: Pregabalin and Visceral Pain 1019mentioning

confidence: 98%

Pregabalin (CI-1008) Inhibits the Trinitrobenzene Sulfonic Acid-Induced Chronic Colonic Allodynia in the Rat

Diop¹,

Raymond²,

Fargeau³

et al. 2002

J Pharmacol Exp Ther

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In human, digestive disorders are often associated with visceral pain. In these pathologies, visceral pain threshold is decreased indicating a visceral hypersensitivity. Pregabalin [CI-1008; S-(ϩ)-3-isobutylgaba] presents antihyperalgesic actions in inflammatory somatic pain models. This study was designed to evaluate 1) the effect of injection of TNBS into the colon on visceral pain threshold, and 2) the antihyperalgesic effect of pregabalin on TNBS-induced chronic colonic allodynia. A significant decrease in the colonic pain threshold was observed in trinitrobenzene sulfonic acid (TNBS)-treated animals (17.8 Ϯ 1.27 versus 43.4 Ϯ 1.98 mm Hg). Pregabalin (30 -200 mg/kg s.c.) and morphine (0.1-1 mg/kg s.c.) showed a dose-related inhibition of TNBS-induced colonic allodynia. Pregabalin did not inhibit the colonic inflammatory effect of TNBS. In normal conditions (control animals), morphine (0.3 mg/kg s.c.) significantly increased the colonic pain threshold, whereas pregabalin (200 mg/kg s.c.) did not modify the colonic pain threshold. Pregabalin suppressed the TNBS-induced colonic allodynia but did not modify the colonic threshold in normal conditions. The ability of pregabalin to block the chronic colonic allodynia indicates that it is effective in abnormal colonic hypersensitivity, suggesting a possible effect in chronic pain in irritable bowel syndrome.

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Section: Pregabalin and Visceral Pain 1019mentioning

confidence: 98%

Pregabalin (CI-1008) Inhibits the Trinitrobenzene Sulfonic Acid-Induced Chronic Colonic Allodynia in the Rat

Diop¹,

Raymond²,

Fargeau³

et al. 2002

J Pharmacol Exp Ther

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“…Furthermore, it has been shown that gabapentin exhibits antinociceptive effects on hyperalgesia (6 -8) and anxiolytic-like effects (8).…”

Section: Introductionmentioning

confidence: 99%

Endogenous GABA Does Not Mediate the Inhibitory Effects of Gabapentin on Spinal Reflexes in Rats

et al. 2004

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Abstract. The novel antiepileptic drug gabapentin was designed as a structural analog of gaminobutyric acid (GABA). However, its mechanism of action remains unclear. In the present study, we investigated the effect of gabapentin on spinal reflexes in anesthetized rats. The monoand polysynaptic reflex potentials were recorded from the ipsilateral L5 ventral root after stimulation of the L5 dorsal root. The dorsal root reflex potential, an index of presynaptic inhibition, was recorded from the ipsilateral L4 dorsal root. In non-spinalized (intact) and spinalized rats, intravenously administered gabapentin reduced the mono-and polysynaptic reflex potentials in a dose-dependent manner. These inhibitory effects of gabapentin were not suppressed by the GABA A antagonist picrotoxin. Moreover, gabapentin also decreased spinal reflexes in spinalized rats depleted of spinal GABA with semicarbazide, an inhibitor of the GABA-synthesizing enzyme. The dorsal root reflex potentials were not affected by gabapentin. These results suggest that endogenous GABA does not mediate the inhibitory effects of gabapentin on spinal reflexes.

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“…However, no agent is fully effective in all patients and undesirable side effects are common (James and Page, 1994;Galer, 1995). In 1996, we described studies suggesting that gabapentin may be useful in the treatment of pain and anxiety (Singh et al, 1996). A number of preclinical reports followed demonstrating that gabapentin, unlike opiates, had no effect on transient physiological pain responses (Field et al, 1997a,b;Hunter et al, 1997;Shimoyama et al, 1997) but possessed antihyperalgesic and antiallodynic properties in animal models of inflammatory, surgical, and neuropathic pain (Xiao and Bennett, 1995;Singh et al, 1996;Field et al, 1997a Field et al, ,b, 1999aHunter et al, 1997;Shimoyama et al, 1997;Hwang and Yaksh, 1997).…”

mentioning

confidence: 99%

“…In 1996, we described studies suggesting that gabapentin may be useful in the treatment of pain and anxiety (Singh et al, 1996). A number of preclinical reports followed demonstrating that gabapentin, unlike opiates, had no effect on transient physiological pain responses (Field et al, 1997a,b;Hunter et al, 1997;Shimoyama et al, 1997) but possessed antihyperalgesic and antiallodynic properties in animal models of inflammatory, surgical, and neuropathic pain (Xiao and Bennett, 1995;Singh et al, 1996;Field et al, 1997aField et al, ,b, 1999aHunter et al, 1997;Shimoyama et al, 1997;Hwang and Yaksh, 1997). In 1998, the first randomized, double blind, placebo-controlled clinical trials were reported that demonstrated that gabapentin showed some efficacy in approximately 50% of patients with postherpetic neuralgia or diabetes-induced neuropathy (Backonja et al, 1998;Row-botham et al, 1998).…”

mentioning

confidence: 99%

Gabapentin and the Neurokinin₁ Receptor Antagonist CI-1021 Act Synergistically in Two Rat Models of Neuropathic Pain

Field¹,

Gonzalez²,

Tallarida³

et al. 2002

J Pharmacol Exp Ther

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The present study examines the effect of combinations of gabapentin (Neurontin) and a selective neurokinin (NK) 1 receptor antagonist, 1-(1H-indol-3-ylmethyl)-1-methyl-2-oxo-2-[(1-phenylethyl)amino]ethyl]-2-benzofuranylmethyl ester (CI-1021), in two models of neuropathic pain. Dose responses to both gabapentin and CI-1021 were performed against static allodynia induced in the streptozocin and chronic constriction injury (CCI) models. Theoretical additive lines were calculated from these data. Dose responses to various fixed dose ratios of a gabapentin/CI-1021 combination were then examined in both models. In the streptozocin model, administration of gabapentin/CI-1021 combinations at fixed dose ratios of 1:1 and 60:1 resulted in an additive effect with dose response similar to the theoretical additive line. However, a synergistic interaction was seen after fixed dose ratios of 10:1, 20:1, and 40:1 with static allodynia completely blocked and the dose responses shifted approximately 8-, 30-, and 10-fold leftward, respectively, from the theoretical additive values. In the CCI model, after fixed dose ratios of 5:1 and 20:1, combinations of gabapentin and CI-1021 produced an additive response. At the fixed dose ratio of 10:1 static allodynia was completely blocked with an approximate 10-fold leftward shift of the dose response from the theoretical additive value, indicating synergy. The combination of gabapentin with a structurally unrelated NK 1 receptor antagonist, (2S,3S)-3-(2-methoxybenzylamino)-2-phenylpiperidine (CP-99,994), also produced synergy, at a fixed dose ratio of 20:1. This ratio completely blocked streptozocin-induced static allodynia and was approximately shifted leftward 5-fold from the theoretical additive value. These data suggest a synergistic interaction between gabapentin and NK 1 receptor antagonists in animal models of neuropathic pain.Neuropathic pain is a consequence of disease or trauma to peripheral nerves or the central nervous system. Thus, this type of pain affects many people with a wide range of ailments (e.g., trauma, diabetes, stroke, postherpetic neuralgia, and cancer). In the clinic, neuropathic pain has proved to be extremely difficult to treat. Neuropathic pain patients can present with a number of different pain subtypes, with allodynic sensations (pain to previously innocuous stimuli) being among the most common and debilitating. Conventional analgesics, such as opiates and nonsteroidal anti-inflammatory drugs have limited therapeutic value in the management of neuropathic pain. This has led to the use of adjuvant analgesics, such as antidepressants and anticonvulsants, for the management of these types of pains. However, no agent is fully effective in all patients and undesirable side effects are common (James and Page, 1994;Galer, 1995). In 1996, we described studies suggesting that gabapentin may be useful in the treatment of pain and anxiety (Singh et al., 1996). A number of preclinical reports followed demonstrating that gabapentin, unlike opiates, had no effect...

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The antiepileptic agent gabapentin (Neurontin) possesses anxiolytic-like and antinociceptive actions that are reversed byd-serine

Cited by 221 publications

References 27 publications

Pregabalin (CI-1008) Inhibits the Trinitrobenzene Sulfonic Acid-Induced Chronic Colonic Allodynia in the Rat

Pregabalin (CI-1008) Inhibits the Trinitrobenzene Sulfonic Acid-Induced Chronic Colonic Allodynia in the Rat

Endogenous GABA Does Not Mediate the Inhibitory Effects of Gabapentin on Spinal Reflexes in Rats

Gabapentin and the Neurokinin₁ Receptor Antagonist CI-1021 Act Synergistically in Two Rat Models of Neuropathic Pain

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The antiepileptic agent gabapentin (Neurontin) possesses anxiolytic-like and antinociceptive actions that are reversed byd-serine

Cited by 221 publications

References 27 publications

Pregabalin (CI-1008) Inhibits the Trinitrobenzene Sulfonic Acid-Induced Chronic Colonic Allodynia in the Rat

Pregabalin (CI-1008) Inhibits the Trinitrobenzene Sulfonic Acid-Induced Chronic Colonic Allodynia in the Rat

Endogenous GABA Does Not Mediate the Inhibitory Effects of Gabapentin on Spinal Reflexes in Rats

Gabapentin and the Neurokinin1 Receptor Antagonist CI-1021 Act Synergistically in Two Rat Models of Neuropathic Pain

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Gabapentin and the Neurokinin₁ Receptor Antagonist CI-1021 Act Synergistically in Two Rat Models of Neuropathic Pain