Gabapentin in the management of reflex sympathetic dystrophy

Mellick, Gary A.; Mellicy, Larry B; Mellick, Larry B.

doi:10.1016/0885-3924(95)00001-f

Cited by 164 publications

(60 citation statements)

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“…Tactile allodynia was not observed in sham-operated rats or in paws contralateral to the nerve ligation (data not shown). Intrathecal gabapentin infusion for 1 week reversed the allodynic state in a dose-dependent manner, consistent with its therapeutic effects after systemic administration in patients with neuropathic pain (Mellick et al, 1995;Rosner et al, 1996) and its spinal action in the same rat neuropathic pain model (Hwang and Yaksh, 1997). Thus, it seems that long-term intrathecal gabapentin infusion does not result in tolerance development.…”

Section: Peripheral But Not Central Axon Injury Induces Marked Upregumentioning

confidence: 54%

“…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).…”

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confidence: 99%

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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: Peripheral But Not Central Axon Injury Induces Marked Upregumentioning

confidence: 54%

mentioning

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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“…In human studies, it consistently provided relief of pain associated with various conditions including postherpetic neuralgia (7), diabetic peripheral neuropathy (12), and complex regional pain syndrome (8). Its efficacy on allodynia and hyperalgesia was also demonstrated in numerous animal studies (2)(3)(4)(5)(6).…”

Section: Discussionmentioning

confidence: 95%

“…In studies on facilitated pain in rats following the formalin test, gabapentin suppress the pain behavior observed during the second phase (5,6). Furthermore, its effectiveness for the treatment of neuropathic pain such as postherpetic neuralgia (7) and complex regional pain syndrome (8) has been reported in human studies.…”

Section: Introductionmentioning

confidence: 99%

Hemodynamic Effects of Gabapentin in Rats

Yoon

Choi

2003

J Korean Med Sci

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Gabapentin has been known to elicit the antinociceptive effect. However, little has been known about the effect of gabapentin on the cardiovascular system. The author's aim of this experiment was to examine the hemodynamic effects of gabapentin. Male Sprague-Dawley rats were used. Intrathecal or intracerebroventricular catheters were implanted and gabapentin was delivered through each catheter or directly into the peritoneal cavity. For hemodynamic measurements, catheters were inserted into the tail artery. Blood pressure and heart rate were measured over 60 min following administration of gabapentin. Intrathecal and intraperitoneal gabapentin did not induce significant changes of hemodynamics over the 60 min compared to the baseline value. Intracerebroventricular gabapentin increased systolic and diastolic blood pressure, but there is no statistically difference in blood pressure change according to the dose.

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“…Furthermore, it has been shown to be efficacious in numerous small clinical studies and case reports in a wide variety of neuropathic pain syndromes, as well as other types of pain (21). Specifically, gabapentin has been clearly demonstrated to be effective for the treatment of neuropathic pain in diabetic neuropathy (22,23), postherpetic neuralgia (24), trigeminal neuralgia (25), painful neuropathy from HIV infection (26), cancer (27)(28)(29), and complex regional pain syndromes (30,31). This supportive evidence, combined with the drug's favourable side-effect profile in various patient groups (including the elderly) and lack of drug interactions, has rendered it an attractive agent for clinical practice.…”

Section: Gabapentinmentioning

confidence: 99%

Gabapentin for acute and chronic post-surgical pain

Melemeni

Staikou

Fassoulaki

2007

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Gabapentin in the management of reflex sympathetic dystrophy

Cited by 164 publications

References 3 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

Hemodynamic Effects of Gabapentin in Rats

Gabapentin for acute and chronic post-surgical pain

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Gabapentin in the management of reflex sympathetic dystrophy

Cited by 164 publications

References 3 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

Hemodynamic Effects of Gabapentin in Rats

Gabapentin for acute and chronic post-surgical pain

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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