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Efficacy of a topical gabapentin gel in a cisplatin paradigm of chemotherapy-induced peripheral neuropathy.
BMC Pharmacol Toxicol. 2019 08 28; 20(1):51.BP

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.

Authors+Show Affiliations

Department of Pharmacy, Sarhad University of Science and Information Technology, Peshawar, Pakistan. Department of Pharmacy, University of Peshawar, Peshawar, 25120, Pakistan.Department of Pharmacy, University of Peshawar, Peshawar, 25120, Pakistan. fazal_subhan@uop.edu.pk. Department of Pharmacy, CECOS University, Hayatabad, Phase 6, Peshawar, Khyber Pakhtunkhwa, Pakistan. fazal_subhan@uop.edu.pk.Department of Pharmacy, University of Peshawar, Peshawar, 25120, Pakistan. Department of Pharmacy, Abasyn University, Peshawar, Pakistan.Cardiff School of Pharmacy and Pharmaceutical Sciences, Cardiff University, Cardiff, CF10 3NU, UK. sewell@cardiff.ac.uk.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31462283

Citation

Shahid, Muhammad, et al. "Efficacy of a Topical Gabapentin Gel in a Cisplatin Paradigm of Chemotherapy-induced Peripheral Neuropathy." BMC Pharmacology & Toxicology, vol. 20, no. 1, 2019, p. 51.
Shahid M, Subhan F, Ahmad N, et al. Efficacy of a topical gabapentin gel in a cisplatin paradigm of chemotherapy-induced peripheral neuropathy. BMC Pharmacol Toxicol. 2019;20(1):51.
Shahid, M., Subhan, F., Ahmad, N., & Sewell, R. D. E. (2019). Efficacy of a topical gabapentin gel in a cisplatin paradigm of chemotherapy-induced peripheral neuropathy. BMC Pharmacology & Toxicology, 20(1), 51. https://doi.org/10.1186/s40360-019-0329-3
Shahid M, et al. Efficacy of a Topical Gabapentin Gel in a Cisplatin Paradigm of Chemotherapy-induced Peripheral Neuropathy. BMC Pharmacol Toxicol. 2019 08 28;20(1):51. PubMed PMID: 31462283.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Efficacy of a topical gabapentin gel in a cisplatin paradigm of chemotherapy-induced peripheral neuropathy. AU - Shahid,Muhammad, AU - Subhan,Fazal, AU - Ahmad,Nisar, AU - Sewell,Robert D E, Y1 - 2019/08/28/ PY - 2018/12/13/received PY - 2019/08/11/accepted PY - 2019/8/30/entrez PY - 2019/8/30/pubmed PY - 2020/2/6/medline KW - Allodynia and heat hypoalgesia KW - Cisplatin KW - Gabapentin KW - Neuropathic pain KW - Topical KW - Topical gel SP - 51 EP - 51 JF - BMC pharmacology & toxicology JO - BMC Pharmacol Toxicol VL - 20 IS - 1 N2 - 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. SN - 2050-6511 UR - https://www.unboundmedicine.com/medline/citation/31462283/Efficacy_of_a_topical_gabapentin_gel_in_a_cisplatin_paradigm_of_chemotherapy_induced_peripheral_neuropathy_ L2 - https://bmcpharmacoltoxicol.biomedcentral.com/articles/10.1186/s40360-019-0329-3 DB - PRIME DP - Unbound Medicine ER -