Gabapentin and pregabalin, but not morphine and amitriptyline, block both static and dynamic components of mechanical allodynia induced by streptozocin in the rat

Abstract

A single injection of streptozocin (50 mg/kg, i.p.) led to the development of static and dynamic allodynia in the rat. The two responses were detected, respectively, by application of pressure using von Frey hairs or lightly stroking the hind paw with a cotton bud. Static allodynia was present in the majority of the animals within 10 days following streptozocin. In contrast, dynamic allodynia took almost twice as long to develop and was only present in approximately 60% of rats. Morphine (1-3 mg/kg, s.c.) and amitriptyline (0.25-2.0 mg/kg, p.o.) dose-dependently blocked static allodynia. However, neither of the compounds was effective against dynamic allodynia. In contrast, gabapentin (10-100 mg/kg, p.o.) and the related compound pregabalin (3-30 mg/kg, p.o.) dose-dependently blocked both types of allodynia. However, the corresponding R-enantiomer (10-100 mg/kg, p.o.) of pregabalin, was found to be inactive. The intrathecal administration of gabapentin dose-dependently (1-100 microg/animal) blocked both static and dynamic allodynia. In contrast, administration of similar doses of gabapentin into the hind paw failed to block these responses. It is suggested that in this model of neuropathic pain dynamic allodynia is mediated by A beta-fibres and the static type involves small diameter nociceptive fibres. These data suggest that gabapentin and pregabalin possess a superior antiallodynic profile than morphine and amitriptyline, and may represent a novel class of therapeutic agents for the treatment of neuropathic pain.

Attenuation of neuropathy-induced allodynia following intraplantar injection of pregabalin

“…Yet, administration of gabapentin into the hind paw failed to block both the static and dynamic allodynia induced by streptozocin in rats. 33 This discrepancy with our study is possibly due to the different animal models (streptozocin vs spinal nerve ligation) and the different types and doses of drugs (gabapentin 1-100 lg/animal vs pregabalin 10-50 mgÁkg -1 ). Pregabalin-related side effects include mild-to-moderate central nervous system disturbances, such as dizziness, somnolence and ataxia, dose-dependent peripheral edema, weight gain, 34,35 myoclonus, 36,37 a cortical negative form of myoclonus, 38 and exacerbation of heart failure.…”

Dynorphin A, kappa opioid receptors and the antinociceptive efficacy of asimadoline in streptozotocin-induced diabetic rats

“…Formalin-evoked hyperalgesia in diabetic rats shares some features with the allodynia present in diabetic animals. These features include prevention by insulin therapy [22] and alleviation by gabapentin [37,38] or a prosaposin-derived peptide [39], but they differ in responsiveness to aldose reductase inhibition [1,22]. In the present study we found that phase 2 of formalin-evoked hyperalgesia in diabetic rats was alleviated by systemic asimadoline and this was partially blocked by systemic or intrathecal nor-BNI, indicating KOR involvement in the mechanism of action of asimadoline.…”

Injury Type-Specific Calcium Channel α2δ-1 Subunit Up-Regulation in Rat Neuropathic Pain Models Correlates with Antiallodynic Effects of Gabapentin

“…Interestingly, vincristine-induced allodynia in Harlan rats is less sensitive to treatment with gabapentin ( Fig. 4E) than that in Holtzman rats to treatment with pregabalin (Nozaki-Taguchi et al, 2001), a similar but more potent antiallodynic drug (Field et al, 1999). It seems that the gabapentin insensitivity in our VIN rats is not due to inadequate dose of the drug because both drugs have similar binding affinities to the ␣ 2 ␦-1 subunit (Suman-Chauhan et al, 1993) and the difference in drug doses between our study (up to 300 mg/kg gabapentin i.p.)…”

“…Spinal administration of gabapentin, a novel anticonvulsant that binds to the ␣ 2 ␦ subunits of the voltage-gated calcium channels in vitro (Marais et al, 2001), suppresses allodynia in neuropathic pain models without general analgesic effects (Hwang and Yaksh, 1997;Abdi et al, 1998;Field et al, 1999). In addition, the potencies of gabapentinoids against neuropathic pain correlate with their sterospecificity and binding affinities at the ␣ 2 ␦ site (Suman-Chauhan et al, 1993;Dissanayake et al, 1997;Hwang and Yaksh, 1997).…”