Efficacy of a topical gabapentin gel in a cisplatin paradigm of chemotherapy-induced peripheral neuropathy

Abstract

Background Chemotherapy induced peripheral neuropathy (CIPN) has been attributed to chemotherapeutic agents such as cisplatin which adversely affect disease outcome leading to increased cancer related morbidity. The clinical efficacy of systemic gabapentin in neuropathic pain management is limited by central side-effects in addition to a scarceness of conclusive evidence of its efficacy in CIPN management. The topical route therefore may provide a relatively safe alternative for neuropathic pain treatment in general and CIPN in particular. Methods Cisplatin induced neuropathic nociception was established in rats after a single weekly cisplatin injection (3.0 mg/kg, intraperitoneally) for 4 weeks. The evoked neuropathic sensation of allodynia was assessed by plantar application of von Frey monofilaments as the paw withdrawal threshold (PWT), whereas the expression of heat-hypoalgesia was determined on a hot-plate as paw withdrawal latency (PWL). Gabapentin gel (10% w/w) was applied three-times daily on the hind paws while in a concurrent systemic study, gabapentin was administered daily (75 mg/kg, intraperitoneally) for 4 weeks. To assess any evidence of neurological adverse symptoms of cisplatin and the central side-effect propensity of systemic or topical gabapentin, evaluation of motor coordination (rotarod test) and gait (footprint analysis) were performed. Results Cisplatin invoked a progressive development of neuropathic hind paw allodynia (decreased PWT, days 7–28) and heat hypoalgesia (increased PWL, days 21–28). Topical gabapentin significantly delayed the expression of both allodynia on protocol days 21 and 28 and heat-hypoalgesia (day 28). Systemic gabapentin displayed a comparative anti-neuropathic predisposition through a sustained suppression of tactile allodynia on days 14 and 21–28 as well as thermal hypoalgesia (days 21 and 28). Systemic gabapentin also impaired motor coordination and gait thus affirming its clinically documented central side effects, but these outcomes were not evident after topical treatment. Conclusions Both topical and systemic gabapentin exhibit a propensity to attenuate CIPN in a cisplatin paradigm. Gabapentin applied topically may therefore provide an adjunctive or alternative route for CIPN management upon cessation of systemic medications due to intolerable side-effects. Electronic supplementary material The online version of this article (10.1186/s40360-019-0329-3) contains supplementary material, which is available to authorized users.

G Protein-Coupled Receptors and Ion Channels Involvement in Cisplatin-Induced Peripheral Neuropathy: A Review of Preclinical Studies

“…Moreover, auxiliary subunits important for Ca V channel function and expression, specifically α1β and α2δ1 subunits of the N-type Ca V channel, were also increased in DRG after cisplatin exposure [87]. In accordance with this data, gabapentin and pregabalin, drugs that bind and inhibit the α2δ1 subunit of Ca V channels, have been shown to diminish neuropathic-like pain associated with cisplatin [89][90][91][92][93]. These data reinforce that the Ca V channels contribute to cisplatin-induced peripheral neuropathy, especially the Ca V 1 and Ca V 2 channel subtypes.…”

Effectiveness of topical gabapentin in the treatment of vulvodynia: a narrative synthesis

“…An analgesic effect was also observed in a rabbit model in which ocular pain was ameliorated following application of gabapentin eye drops ( 40 ). Furthermore, gabapentin 10% gel attenuated neuropathic allodynia and heat-hypoalgesia in a cisplatin rat model of chemotherapy-induced peripheral neuropathy ( 41 ). Topical gabapentin 10% gel also significantly allayed hyperalgesia and allodynia in a rat chronic sciatic nerve constriction injury neuropathic pain model ( 26 ).…”

Topical gabapentin solution for the management of burning mouth syndrome: A retrospective study

“…Nociceptors in mucosal barriers contain various types of receptors that bind different ligands which influence the generation of pain transmitting action potentials. Topical gabapentin could traverse tissue and increase the nociceptive threshold by stabilizing the membranes of specific nociceptors [24]. The topical pharmacological approach for the management of BMS was initially introduced by Gremeau-Richard et al [25].…”