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Intrathecal delivery of farnesyl thiosalicylic acid and GW 5074 attenuates hyperalgesia and allodynia in chronic constriction injury-induced neuropathic pain in rats.
Neurol Sci. 2013 Mar; 34(3):297-304.NS

Abstract

The role of mitogen-activated protein kinase (MAPK) family has been well defined in neuropathic pain. Ras and c-Raf constitute an important part of MAP kinase family as Ras/Raf/MEK/ERK2 signaling cascade. The present study was designed to investigate the analgesic potential of farnesyl thiosalicylic acid, a novel Ras inhibitor, and GW 5074, a selective c-Raf1 inhibitor, in chronic constriction-induced injury (CCI)-induced peripheral neuropathic pain. Neuropathic pain was induced by placing four loose ligatures around the sciatic nerve. The development of pain was assessed on 14th day in terms of cold allodynia; mechanical hyperalgesia and mechanical allodynia by performing acetone test, pinprick and Von Frey tests, respectively. Farnesyl thiosalicylic acid (2.5, 5 and 10 μg) and GW 5074 (1, 2 and 4 μg) were injected intrathecally on 14th day following nerve ligature to assess their analgesic potential in CCI model. Nerve ligature-induced CCI produced significant neuropathic pain manifestations in terms of cold and mechanical allodynia, and mechanical hyperalgesia. Single intrathecal administration of farnesyl thiosalicylic acid (5 and 10 μg) as well as GW 5074 (2 and 4 μg) significantly attenuated CCI-induced hyperalgesia and allodynia. The analgesic effects of farnesyl thiosalicylic acid and GW 5074 in CCI model suggests that pharmacological inhibition of Ras and c-Raf-1 signaling may be potentially useful for managing neuropathic pain.

Authors+Show Affiliations

Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala, 147002 Punjab, India.No affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

22382741

Citation

Jaggi, Amteshwar Singh, and Nirmal Singh. "Intrathecal Delivery of Farnesyl Thiosalicylic Acid and GW 5074 Attenuates Hyperalgesia and Allodynia in Chronic Constriction Injury-induced Neuropathic Pain in Rats." Neurological Sciences : Official Journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology, vol. 34, no. 3, 2013, pp. 297-304.
Jaggi AS, Singh N. Intrathecal delivery of farnesyl thiosalicylic acid and GW 5074 attenuates hyperalgesia and allodynia in chronic constriction injury-induced neuropathic pain in rats. Neurol Sci. 2013;34(3):297-304.
Jaggi, A. S., & Singh, N. (2013). Intrathecal delivery of farnesyl thiosalicylic acid and GW 5074 attenuates hyperalgesia and allodynia in chronic constriction injury-induced neuropathic pain in rats. Neurological Sciences : Official Journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology, 34(3), 297-304. https://doi.org/10.1007/s10072-012-0991-3
Jaggi AS, Singh N. Intrathecal Delivery of Farnesyl Thiosalicylic Acid and GW 5074 Attenuates Hyperalgesia and Allodynia in Chronic Constriction Injury-induced Neuropathic Pain in Rats. Neurol Sci. 2013;34(3):297-304. PubMed PMID: 22382741.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Intrathecal delivery of farnesyl thiosalicylic acid and GW 5074 attenuates hyperalgesia and allodynia in chronic constriction injury-induced neuropathic pain in rats. AU - Jaggi,Amteshwar Singh, AU - Singh,Nirmal, Y1 - 2012/03/02/ PY - 2011/12/01/received PY - 2012/02/17/accepted PY - 2012/3/3/entrez PY - 2012/3/3/pubmed PY - 2013/9/5/medline SP - 297 EP - 304 JF - Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology JO - Neurol Sci VL - 34 IS - 3 N2 - The role of mitogen-activated protein kinase (MAPK) family has been well defined in neuropathic pain. Ras and c-Raf constitute an important part of MAP kinase family as Ras/Raf/MEK/ERK2 signaling cascade. The present study was designed to investigate the analgesic potential of farnesyl thiosalicylic acid, a novel Ras inhibitor, and GW 5074, a selective c-Raf1 inhibitor, in chronic constriction-induced injury (CCI)-induced peripheral neuropathic pain. Neuropathic pain was induced by placing four loose ligatures around the sciatic nerve. The development of pain was assessed on 14th day in terms of cold allodynia; mechanical hyperalgesia and mechanical allodynia by performing acetone test, pinprick and Von Frey tests, respectively. Farnesyl thiosalicylic acid (2.5, 5 and 10 μg) and GW 5074 (1, 2 and 4 μg) were injected intrathecally on 14th day following nerve ligature to assess their analgesic potential in CCI model. Nerve ligature-induced CCI produced significant neuropathic pain manifestations in terms of cold and mechanical allodynia, and mechanical hyperalgesia. Single intrathecal administration of farnesyl thiosalicylic acid (5 and 10 μg) as well as GW 5074 (2 and 4 μg) significantly attenuated CCI-induced hyperalgesia and allodynia. The analgesic effects of farnesyl thiosalicylic acid and GW 5074 in CCI model suggests that pharmacological inhibition of Ras and c-Raf-1 signaling may be potentially useful for managing neuropathic pain. SN - 1590-3478 UR - https://www.unboundmedicine.com/medline/citation/22382741/Intrathecal_delivery_of_farnesyl_thiosalicylic_acid_and_GW_5074_attenuates_hyperalgesia_and_allodynia_in_chronic_constriction_injury_induced_neuropathic_pain_in_rats_ L2 - https://link.springer.com/10.1007/s10072-012-0991-3 DB - PRIME DP - Unbound Medicine ER -