title: Influence of capsaicin cream in rats with peripheral neuropathy.
abstract: We investigated the effect of topical application of capsaicin cream on withdrawal latency in the hind foot of rat in response to radiant heat in an experimental model of neuropathic pain. A neuropathic state was induced by loose ligation of the sciatic nerve with chromic gut suture. A marked thermal hyperalgesia was observed in response to heat stimulus applied to the operated side from 3 days through 2 weeks, followed by a gradual return to the control level by 35 days after surgery. Capsaicin cream applied to both the bilateral hind instep and sole once a day for a continuous period of 2 weeks or 4 weeks alleviated thermal hyperalgesia in a dose-dependent manner. A remarkable effect was observed 2 weeks after the start of the application and this effect proved to be reversible. On the other hand, in sham-operated animals when capsaicin cream was applied once daily from day 7 after the sham operation, from 1 day through 3 weeks following capsaicin application, withdrawal latency of the sham-operated paws of the capsaicin-treated group was significantly increased as compared to that of the vehicle cream-treated group. The effects of antagonists of glutamate receptor and tachykinin receptors were investigated 7 days post surgery. Pretreatment with MK-801 (0.5 mg kg(-1), i.p.), but not with CNQX (0.5 mg kg(-1), i.p.), reversed the thermal hyperalgesia following nerve injury. Neither of RP67580 (1--10 mg kg(-1), i.p.) nor SR48968 (1--10 mg kg(-1), i.p.) had any effect on the withdrawal latency in the injured and non-injured hind paw. These results suggest that although the manifestation of effectiveness may be delayed by changes in networks of neurotransmitters related to the nociceptive pathways following nerve injury, longer-term repetitive application of capsaicin cream has a significant therapeutic effect on subjects with painful peripheral neuropathy.
authors.affiliation: Central Research Laboratory of Maruishi Pharmaceutical Co., LTD., 2-2-18 Imazunaka, Tsurumi-ku, Osaka 538-0042, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Yoshimura
authors.forename: N
authors.initials: N
authors.lastname: Yonehara
mesh_terms: D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D002211:Capsaicin / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D002351:Carrageenan; D004195:Disease Models, Animal; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D006930:Hyperalgesia / Q000139:chemically induced* / Q000150:complications / Q000188:drug therapy; D007211:Indoles / Q000494:pharmacology; D054833:Isoindoles; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology; D010146:Pain / Q000188:drug therapy; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced* / Q000150:complications; D010880:Piperidines / Q000494:pharmacology; D011184:Postoperative Period; D051381:Rats; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000187:drug effects / Q000502:physiology; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology; D013997:Time Factors
chemical_list: D000700:Analgesics; D001549:Benzamides; D018691:Excitatory Amino Acid Antagonists; D007211:Indoles; D054833:Isoindoles; D018696:Neuroprotective Agents; D010880:Piperidines; C071693:7,7-diphenyl-2-(1-imino-2-(2-methoxyphenyl)ethyl)perhydroisoindol-4-one; D016291:Dizocilpine Maleate; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; C073839:SR 48968; D002351:Carrageenan; D002211:Capsaicin