Gabapentin (Neurontin) for Chemo pain neuropathy

[Guest guest]

Neuroscience. 2006 Nov 1

Chemotherapy-evoked painful peripheral neuropathy: analgesic effects

of gabapentin and effects on expression of the alpha-2-delta type-1

calcium channel subunit.

Xiao W, Boroujerdi A, GJ, Luo ZD.

Department of Anesthesia, Anesthesia Research Unit, McGill

University, 3655 Promenade Sir Osler (McIntyre 1202),

Montreal, Quebec, Canada H3G 1Y6.

Chemotherapeutics in the taxane and vinca-alkaloid classes sometimes

produce a painful peripheral neuropathy for which there is no

validated treatment. Experiments with rat models of paclitaxel- and

vincristine-evoked pain suggest that these conditions may not

respond to all of the analgesics that have efficacy in other models

of painful peripheral neuropathy.

We tested gabapentin as a potential analgesic for paclitaxel- and

vincristine-evoked pain. We used a repeated dosing paradigm because

there are precedents showing that repeated drug exposure may be

necessary to demonstrate analgesia in neuropathic pain models.

Gabapentin is believed to work via binding to voltage-gated calcium

channels that contain the alpha-2-delta type-1 (alpha(2)delta-1)

subunit, and the expression of this subunit is known to be increased

in some painful peripheral neuropathy models. Thus we also examined

whether the paclitaxel-evoked pain syndrome was accompanied by an

alpha(2)delta-1 increase, and whether gabapentin had any effect on

subunit expression.

We found that the paclitaxel- and vincristine-evoked mechano-

allodynia and mechano-hyperalgesia were significantly reduced by

gabapentin, but only with repeated dosing. Paclitaxel-evoked painful

peripheral neuropathy was associated with an increased expression of

the alpha(2)delta-1 subunit in the spinal dorsal horn, but not in

the dorsal root ganglia. The spinal cord increase was normalized by

repeated gabapentin injections.

Together, these findings suggest that repeated dosing with

gabapentin may be beneficial in patients with chemotherapy-evoked

painful peripheral neuropathy and that gabapentin's mechanisms of

action may include normalization of the nerve injury-evoked increase

in calcium channel alpha(2)delta-1 subunit expression.