The Effect of Gabapentin on Neuropathic Pain

Rosenberg, Jack M.; Harrell, Colleen; Ristic, Helen; Werner, Robert A.; Rosayro, A. de

doi:10.1097/00002508-199709000-00011

Cited by 195 publications

(96 citation statements)

References 11 publications

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“…Recent preclinical studies suggest a role for the ␣ 2 ␦ subunit in neuropathic pain processing. Gabapentin, an anticonvulsant drug found to be effective against clinical neuropathic pain states (Mellick et al, 1995;Rosner et al, 1996;Mellick and Mellick, 1997;Rosenberg et al, 1997;Backonja et al, 1998;Rowbotham et al, 1998), also exerts a spinal action in preclinical neuropathic pain models (Hwang and Yaksh, 1997;Abdi et al, 1998) and yet lacks general analgesic properties (Field et al, 1997). Gabapentin binds with high affinity to the ␣ 2 ␦ subunit in vitro (Gee et al, 1996).…”

Section: Abstract: ␣ 2 ␦ Calcium Channel Subunit; Peripheral Nerve Imentioning

confidence: 99%

Upregulation of Dorsal Root Ganglion α₂δ Calcium Channel Subunit and Its Correlation with Allodynia in Spinal Nerve-Injured Rats

et al. 2001

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Peripheral nerve injury can lead to a persistent neuropathic pain state in which innocuous tactile stimulation elicits pain behavior (tactile allodynia). Spinal administration of the anticonvulsant gabapentin suppresses allodynia by an unknown mechanism. In vitro studies indicate that gabapentin binds to the ␣ 2 ␦-1 (hereafter referred to as ␣ 2 ␦) subunit of voltage-gated calcium channels. We hypothesized that nerve injury may result in altered ␣ 2 ␦ subunit expression in spinal cord and dorsal root ganglia (DRGs) and that this change may play a role in neuropathic pain processing. Using a rat neuropathic pain model in which gabapentin-sensitive tactile allodynia develops after tight ligation of the left fifth and sixth lumbar spinal nerves, we found a Ͼ17-fold, time-dependent increase in ␣ 2 ␦ subunit expression in DRGs ipsilateral to the nerve injury. Marked ␣ 2 ␦ subunit upregulation was also evident in rats with unilateral sciatic nerve crush, but not dorsal rhizotomy, indicating a peripheral origin of the expression regulation. The increased ␣ 2 ␦ subunit expression preceded the allodynia onset and diminished in rats recovering from tactile allodynia. RNase protection experiments indicated that the DRG ␣ 2 ␦ regulation was at the mRNA level. In contrast, calcium channel ␣ 1B and ␤ 3 subunit expression was not co-upregulated with the ␣ 2 ␦ subunit after nerve injury. These data suggest that DRG ␣ 2 ␦ regulation may play an unique role in neuroplasticity after peripheral nerve injury that may contribute to allodynia development. Key words: ␣ 2 ␦ calcium channel subunit; peripheral nerve injury; rhizotomy; allodynia; dorsal root ganglia; spinal cord; sensory neuronsPeripheral nerve injury may lead to neuropathic syndromes characterized by both spontaneous and evoked painful sensations. Allodynia, or an exaggerated response to otherwise innocuous tactile stimuli, is considered both a hallmark and the most troublesome of these syndromes (Price et al., 1989;Wahren and Torebjork, 1992;Koltzenburg et al., 1994). The molecular mechanisms of neuropathic pain states are not clear. It has been hypothesized that disordered sensory processing arises from long-term changes in the function of sensory afferents and the organization of sensory input into the dorsal horn (Coderre et al., 1993;Woolf and Doubell, 1994).Pharmacological evidence suggests that spinal N-type voltagegated calcium channels (N-VGCCs) play a role in neuropathic pain transduction. Intrathecal delivery of N-type ( -conopeptides), but not L-or P-type, VGCC antagonists suppresses allodynia in neuropathic rat models (Chaplan et al., 1994b;Calcutt and Chaplan, 1997). Autoradiographic studies showed the highest density of conopeptide-binding sites in the spinal dorsal horn (lamina I and II) where primary afferents terminate (Kerr et al., 1988;Takemura et al., 1989). N-VGCCs are also found in dorsal root ganglion (DRG) neurons where they are differentially modulated after sciatic nerve damage (Abdulla and Smith, 1997).High-threshold neuronal VGCCs contain thr...

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Section: Abstract: ␣ 2 ␦ Calcium Channel Subunit; Peripheral Nerve Imentioning

confidence: 99%

Upregulation of Dorsal Root Ganglion α₂δ Calcium Channel Subunit and Its Correlation with Allodynia in Spinal Nerve-Injured Rats

et al. 2001

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“…Systemic therapies of choice are tricyclic antidepressants [40]. anticonvulsant agents [41], alpha blocking agents [42], and systemic lidocaine [43].…”

Section: Discussionmentioning

confidence: 99%

Ramsay-Hunt syndrome complicating osteonecrosis of edentulous maxilla and mandible: report of a rare case

Badjate

Cariappa

Shenoi

et al. 2009

J. Maxillofac. Oral Surg.

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Review of literature revealed atleast 30 cases of post herpes zoster osteonecrosis of maxilla or mandible. To our knowledge this is a first reported case of Ramsay-Hunt syndrome with post herpetic neuralgia and post herpes zoster osteonecrosis of edentulous maxilla and mandible. We have briefly reviewed the pathophysiology and management of post herpes zoster osteonecrosis and post herpetic neuralgia.

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“…32,33 A summary of selected published studies on this subject appears in Table 2. [27][28][29][30][31][32][33] Morello et al demonstrated that there is no statistically significant difference between amitriptyline and gabapentin in the treatment of diabetics with peripheral neuropathic pain, as measured by pain scales and global pain scores. 34 In this study, 21 diabetic patients with stable glycemic control received either gabapentin or amitriptyline for 6 weeks and then crossed over to the other arm of therapy for 6 additional weeks, with a 1-week wash-out period between therapies.…”

Section: Gabapentin In the Treatment Of Pain Syndromes Peripheral Nementioning

confidence: 99%

Examination of the Evidence for Off-Label Use of Gabapentin

Mack¹

2003

JMCP

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The Effect of Gabapentin on Neuropathic Pain

Abstract: Gabapentin may be a useful adjunct for treating neuropathic pain with a minimum of side effects. Particular advantage may be gained with the use of this drug for postherpetic neuralgia and direct peripheral nerve injuries.

Cited by 195 publications

References 11 publications

Upregulation of Dorsal Root Ganglion α₂δ Calcium Channel Subunit and Its Correlation with Allodynia in Spinal Nerve-Injured Rats

Upregulation of Dorsal Root Ganglion α₂δ Calcium Channel Subunit and Its Correlation with Allodynia in Spinal Nerve-Injured Rats

Ramsay-Hunt syndrome complicating osteonecrosis of edentulous maxilla and mandible: report of a rare case

Examination of the Evidence for Off-Label Use of Gabapentin

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The Effect of Gabapentin on Neuropathic Pain

Abstract: Gabapentin may be a useful adjunct for treating neuropathic pain with a minimum of side effects. Particular advantage may be gained with the use of this drug for postherpetic neuralgia and direct peripheral nerve injuries.

Cited by 195 publications

References 11 publications

Upregulation of Dorsal Root Ganglion α2δ Calcium Channel Subunit and Its Correlation with Allodynia in Spinal Nerve-Injured Rats

Upregulation of Dorsal Root Ganglion α2δ Calcium Channel Subunit and Its Correlation with Allodynia in Spinal Nerve-Injured Rats

Ramsay-Hunt syndrome complicating osteonecrosis of edentulous maxilla and mandible: report of a rare case

Examination of the Evidence for Off-Label Use of Gabapentin

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Product

Resources

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Upregulation of Dorsal Root Ganglion α₂δ Calcium Channel Subunit and Its Correlation with Allodynia in Spinal Nerve-Injured Rats

Upregulation of Dorsal Root Ganglion α₂δ Calcium Channel Subunit and Its Correlation with Allodynia in Spinal Nerve-Injured Rats