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Gabapentin and its salicylaldehyde derivative alleviate allodynia and hypoalgesia in a cisplatin-induced neuropathic pain model.
Eur J Pharmacol. 2017 Nov 05; 814:302-312.EJ

Abstract

Cisplatin is an effective chemotherapeutic agent indicated in cancer chemotherapy. However, its clinical use is associated with peripheral neuropathy that invariably impairs patient quality of life. Gabapentin (GBP) is an effective analgesic for neuropathic pain conditions but its clinical efficacy in cisplatin-induced neuropathic pain (CINP) is limited, in addition to generating unwanted side-effects. In this study, a gabapentin-salicylaldehyde derivative [gabapentsal (GPS)] was synthesized and evaluated to explore any potential benefit in comparison with GBP in a rat model of CIPN. Administration of cisplatin (3.0mg/kg/week, i.p.) for five consecutive weeks generated reproducible mechanical-allodynia (decreased paw withdrawal threshold to von Frey filament application; PWT, g) and thermal hypoalgesia (increased nociceptive reaction latency in the hot plate paradigm; s). Treatment with GBP or its derivative on the 37th day of the experimental protocol, dose dependently attenuated cisplatin-induced nocifensive behaviors. Accordingly, doses of GBP (50-100mg/kg, i.p.) and GPS (25-100mg/kg, i.p.) suppressed the expression of CINP by normalizing the PWT and hot plate response latency 1h and 3h post administration. In the rotarod paradigm, GBP at all doses markedly impaired motor performance, whilst GPS was devoid of motor incoordination except at the highest dose, when a mild impairment occurred. Salicylaldehyde alone had no effect on CINP or rotarod performance and neither was there any synergism when coadministered with GBP. These findings suggest that both GBP and GPS have beneficial effects in the neuropathic pain model though GPS may be potentially more useful in the management of CINP.

Authors+Show Affiliations

Department of Pharmacy, University of Peshawar, Peshawar 25120, Khyber Pakhtunkhwa, Pakistan. Electronic address: nisarahmadsatal@yahoo.com.Department of Pharmacy, University of Peshawar, Peshawar 25120, Khyber Pakhtunkhwa, Pakistan. Electronic address: fazal_subhan@upesh.edu.pk.Department of Pharmacy, Sarhad University of Science and Information Technology, Peshawar, Pakistan. Electronic address: islanaz@yahoo.com.Department of Pharmacy, University of Peshawar, Peshawar 25120, Khyber Pakhtunkhwa, Pakistan; Department of Pharmacy, Sarhad University of Science and Information Technology, Peshawar, Pakistan. Electronic address: shahidsalim_2002@hotmail.com.Department of Chemistry, Fudan University, Shanghai, China. Electronic address: faizurrahman@fudan.edu.cn.Cardiff School of Pharmacy and Pharmaceutical Sciences, Cardiff University, Cardiff CF10 3NB, UK. Electronic address: sewell@cardiff.ac.uk.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28865678

Citation

Ahmad, Nisar, et al. "Gabapentin and Its Salicylaldehyde Derivative Alleviate Allodynia and Hypoalgesia in a Cisplatin-induced Neuropathic Pain Model." European Journal of Pharmacology, vol. 814, 2017, pp. 302-312.
Ahmad N, Subhan F, Islam NU, et al. Gabapentin and its salicylaldehyde derivative alleviate allodynia and hypoalgesia in a cisplatin-induced neuropathic pain model. Eur J Pharmacol. 2017;814:302-312.
Ahmad, N., Subhan, F., Islam, N. U., Shahid, M., Rahman, F. U., & Sewell, R. D. E. (2017). Gabapentin and its salicylaldehyde derivative alleviate allodynia and hypoalgesia in a cisplatin-induced neuropathic pain model. European Journal of Pharmacology, 814, 302-312. https://doi.org/10.1016/j.ejphar.2017.08.040
Ahmad N, et al. Gabapentin and Its Salicylaldehyde Derivative Alleviate Allodynia and Hypoalgesia in a Cisplatin-induced Neuropathic Pain Model. Eur J Pharmacol. 2017 Nov 5;814:302-312. PubMed PMID: 28865678.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Gabapentin and its salicylaldehyde derivative alleviate allodynia and hypoalgesia in a cisplatin-induced neuropathic pain model. AU - Ahmad,Nisar, AU - Subhan,Fazal, AU - Islam,Nazar Ul, AU - Shahid,Muhammad, AU - Rahman,Faiz Ur, AU - Sewell,Robert D E, Y1 - 2017/09/01/ PY - 2017/05/08/received PY - 2017/08/03/revised PY - 2017/08/24/accepted PY - 2017/9/4/pubmed PY - 2018/6/2/medline PY - 2017/9/4/entrez KW - Chemotherapy-induced neuropathic pain KW - Gabapentin (PubChem CID: 3446) KW - Gabapentsal KW - Motor incoordination KW - Peripheral neuropathic pain KW - Rat neuropathic pain model KW - Salicylaldehyde (PubChem CID: 6998) KW - Thermal hypoalgesia SP - 302 EP - 312 JF - European journal of pharmacology JO - Eur J Pharmacol VL - 814 N2 - Cisplatin is an effective chemotherapeutic agent indicated in cancer chemotherapy. However, its clinical use is associated with peripheral neuropathy that invariably impairs patient quality of life. Gabapentin (GBP) is an effective analgesic for neuropathic pain conditions but its clinical efficacy in cisplatin-induced neuropathic pain (CINP) is limited, in addition to generating unwanted side-effects. In this study, a gabapentin-salicylaldehyde derivative [gabapentsal (GPS)] was synthesized and evaluated to explore any potential benefit in comparison with GBP in a rat model of CIPN. Administration of cisplatin (3.0mg/kg/week, i.p.) for five consecutive weeks generated reproducible mechanical-allodynia (decreased paw withdrawal threshold to von Frey filament application; PWT, g) and thermal hypoalgesia (increased nociceptive reaction latency in the hot plate paradigm; s). Treatment with GBP or its derivative on the 37th day of the experimental protocol, dose dependently attenuated cisplatin-induced nocifensive behaviors. Accordingly, doses of GBP (50-100mg/kg, i.p.) and GPS (25-100mg/kg, i.p.) suppressed the expression of CINP by normalizing the PWT and hot plate response latency 1h and 3h post administration. In the rotarod paradigm, GBP at all doses markedly impaired motor performance, whilst GPS was devoid of motor incoordination except at the highest dose, when a mild impairment occurred. Salicylaldehyde alone had no effect on CINP or rotarod performance and neither was there any synergism when coadministered with GBP. These findings suggest that both GBP and GPS have beneficial effects in the neuropathic pain model though GPS may be potentially more useful in the management of CINP. SN - 1879-0712 UR - https://www.unboundmedicine.com/medline/citation/28865678/Gabapentin_and_its_salicylaldehyde_derivative_alleviate_allodynia_and_hypoalgesia_in_a_cisplatin_induced_neuropathic_pain_model_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-2999(17)30548-4 DB - PRIME DP - Unbound Medicine ER -