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B2 bradykinin receptor‐expressing nociceptors are differentially sensitive to the microtubule‐targeting agent, paclitaxel (659.3)
Author(s) -
LoCoco Peter,
Scofield Harrison,
Chavera Teresa,
Mooberry Susan,
Berg Kelly,
Clarke William
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.659.3
Subject(s) - nociceptor , allodynia , bradykinin , medicine , transient receptor potential channel , nociception , cold sensitivity , pharmacology , receptor , hyperalgesia , anesthesia , chemistry , biochemistry , mutant , gene
Paclitaxel (TAX) produces debilitating peripheral neuropathy accompanied by pain. Interestingly, patients complain more frequently of increased sensitivity to cold but not hot temperatures. Thus, we hypothesize that TAX differentially damages functional subpopulations of peripheral pain‐sensing neurons (i.e. nociceptors). Here, we evaluated TAX effects on bradykinin (BK) receptor‐expressing nociceptors. Paw withdrawal latency (PWL) to a heat or cold stimulus was determined following TAX treatment. PWL of TAX rats to cold was decreased, whereas PWL to heat was increased, suggesting that TAX differentially affected cold‐ and heat‐responsive nociceptors. We then evaluated PWL to cold and heat following i.pl. BK injections. As expected, BK produced a transient cold and heat allodynia in vehicle rats. By contrast, TAX treatment reduced heat, but prolonged cold allodynia. Treatment of primary nociceptor cultures with TAX produced a time‐dependent, tri‐phasic effect on BK‐stimulated phospholipase C activity that was blocked by a B 2 , but not B 1 , antagonist. Taken together, these data suggest that nociceptor subpopulations are differentially sensitive to TAX. Understanding why some nociceptors are resistant to effects by TAX could reveal novel treatment/preventative strategies for chemotherapy‐induced peripheral neuropathy. Grant Funding Source : Supported by USPS grant 8ULITR000149, Greehey Fellowship, and Translational Science Training Program