Backonja M, Beydoun A, Edwards KR, Schwartz SL, Fonseca V, Hes M, LaMoreaux L, Garofalo E: Gabapentin for the symptomatic treatment of painful neuropathy in patients with diabetes mellitus: A randomized controlled trial. JAMA 280: 1831-6

Department of Neurology, University of Wisconsin, Madison 53792, USA.
JAMA The Journal of the American Medical Association (Impact Factor: 35.29). 01/1999; 280(21):1831-6. DOI: 10.1001/jama.280.21.1831
Source: PubMed


Pain is the most disturbing symptom of diabetic peripheral neuropathy. As many as 45% of patients with diabetes mellitus develop peripheral neuropathies.
To evaluate the effect of gabapentin monotherapy on pain associated with diabetic peripheral neuropathy.
Randomized, double-blind, placebo-controlled, 8-week trial conducted between July 1996 and March 1997.
Outpatient clinics at 20 sites.
The 165 patients enrolled had a 1- to 5-year history of pain attributed to diabetic neuropathy and a minimum 40-mm pain score on the Short-Form McGill Pain Questionnaire visual analogue scale.
Gabapentin (titrated from 900 to 3600 mg/d or maximum tolerated dosage) or placebo.
The primary efficacy measure was daily pain severity as measured on an 11-point Likert scale (0, no pain; 10, worst possible pain). Secondary measures included sleep interference scores, the Short-Form McGill Pain Questionnaire scores, Patient Global Impression of Change and Clinical Global Impression of Change, the Short Form-36 Quality of Life Questionnaire scores, and the Profile of Mood States results.
Eighty-four patients received gabapentin and 70 (83%) completed the study; 81 received placebo and 65 (80%) completed the study. By intent-to-treat analysis, gabapentin-treated patients' mean daily pain score at the study end point (baseline, 6.4; end point, 3.9; n = 82) was significantly lower (P<.001) compared with the placebo-treated patients' end-point score (baseline, 6.5; end point, 5.1; n = 80). All secondary outcome measures of pain were significantly better in the gabapentin group than in the placebo group. Additional statistically significant differences favoring gabapentin treatment were observed in measures of quality of life (Short Form-36 Quality of Life Questionnaire and Profile of Mood States). Adverse events experienced significantly more frequently in the gabapentin group were dizziness (20 [24%] in the gabapentin group vs 4 [4.9%] in the control group; P<.001) and somnolence (19 [23%] in the gabapentin group vs 5 [6%] in the control group; P = .003). Confusion was also more frequent in the gabapentin group (7 [8%] vs 1 [1.2%]; P = .06).
Gabapentin monotherapy appears to be efficacious for the treatment of pain and sleep interference associated with diabetic peripheral neuropathy and exhibits positive effects on mood and quality of life.

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    • "There have been many studies on the treatment of neuropathic pain, and many drugs, such as nonsteroidal anti-inflammatory drugs, opiates, antidepressants, antiepileptics, etc., have been found to be effective in treating neuropathic pain. Gabapentin was found to be effective in clinical trials for diabetic neuropathy, post-herpetic neuralgia, neuropathic pain after SCI, cancer, and other neuropathic pain [25,26,27,28]. Pregabalin, an antiepileptic drug similar to gabapentin, was found to be effective in studies on diabetic neuropathy, post-herpetic neuralgia, and neuropathic pain after SCI [29,30,31,32]. "
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    ABSTRACT: Objective To characterize neuropathic pain in patients with spinal cord injury (SCI) according to classification used in the study by Baron et al. (Baron classification), a classification of neuropathic pain based on the mechanism. To also compare the patterns of neuropathic pain in SCI patients with those in patients with other etiologies and to determine the differences in patterns of neuropathic pain between the etiologies. Methods This was a descriptive cross-sectional study. We used the Baron classification to investigate the characteristics of neuropathic pain in SCI. Sixty-one SCI patients with neuropathic pain (The Leeds assessment of neuropathic symptoms and signs score ≥12) were enrolled in this study between November 2012 and August 2013, after excluding patients <20 of age, patients with visual analog scale (VAS) score <3, pregnant patients, and patients with systemic disease or pain other than neuropathic pain. Results The most common pain characteristic was pricking pain followed by electrical pain and numbness. The mean VAS score of at-level neuropathic pain was 7.51 and that of below-level neuropathic pain was 6.83. All of the patients suffered from rest pain, but 18 (54.6%) patients with at-level neuropathic pain and 20 (50.0%) patients with below-level neuropathic pain suffered from evoked pain. There was no significant difference in between at-level and below-level neuropathic pains. Conclusion The result was quite different from the characteristics of post-herpetic neuralgia, but it was similar to the characteristics of diabetic neuropathy as shown in the study by Baron et al., which means that sensory nerve deafferentation may be the most common pathophysiologic mechanism of neuropathic pain after SCI. Since in our study, we included short and discrete symptoms and signs based on diverse mechanisms, our results could be helpful for determining further evaluation and treatment.
    Full-text · Article · Jun 2014 · Annals of Rehabilitation Medicine
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    • "Backonja et al. investigated the effect of gabapentin monotherapy on pain associated with diabetic peripheral neuropathy by titrating from 900 to 3600 mg per day or maximum tolerated dosage or placebo [12]. The safety of gabapentin was determined by using adverse event data (occurrence, intensity, and relationship to gabapentin) and the results of physical and neurological examination, including peripheral sensory examinations. "
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    ABSTRACT: Gabapentin (1-aminomethyl-cyclohexaneacetic acid) is an amino acid that has the structure of the neurotransmitter γ -aminobutyric acid (GABA). It is a novel drug used for the treatment of postoperative pain with antihyperalgesic properties and a unique mechanism of action. Gabapentin and the related, more potent compound pregabalin have been shown to be beneficial in the treatment of neuropathic pain as well as postoperative pain following spinal surgery and hysterectomy. This study reviews five aspects of gabapentin: (1) chemical and structural characteristics; (2) pharmacokinetics and pharmacodynamics; (3) application in acute pain management; (4) adverse effects; and (5) drug safety. Overall, gabapentin has been reported to be a safe and efficacious drug for the treatment of postoperative pain.
    Full-text · Article · Apr 2014
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    • "Animal models were employed in the preclinical development of pregabalin, but an area of potential bias is that the findings from these preclinical studies only started to appear (Field et al., 1997) at about the same time as the pivotal clinical trials of gabapentin (Backonja et al., 1998; Rowbotham et al., 1998; Rice and Maton, 2001). The paucity of new analgesic drugs contrasts with the amount of preclinical research reported. "
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    ABSTRACT: Neuropathic pain remains an area of considerable unmet clinical need. Research based on preclinical animal models has failed to deliver truly novel treatment options, questioning the predictive value of these models. This review addresses the shortcomings of rodent in vivo models commonly used in the field and highlights approaches which could increase their predictivity, including more clinically relevant assays, outcome measures and animal characteristics. The methodological quality of animal studies also needs to be improved. Low internal validity and incomplete reporting lead to a waste of valuable research resources and animal lives, and ultimately prevent an objective assessment of the true predictivity of in vivo models.
    Full-text · Article · Feb 2014 · British Journal of Pharmacology
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