• Chi Li, Hiroshi Sekiyama, Masakazu Hayashida, Kenji Takeda, Toshinobu Sumida, Shigehito Sawamura, Yoshitsugu Yamada, Hideko Arita, and Kazuo Hanaoka.
• Department of Anesthesiology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
• Anesthesiology. 2007 Sep 1; 107 (3): 486-94.

BackgroundClonidine can effectively reduce pain and/or hypersensitivity. However, the antihypersensitivity effects of clonidine topically applied in cream (CC) have not been investigated. The authors evaluated effects of topical application of CC on pain behaviors and spinal Fos-like immunoreactivity in rats with hypersensitivity.MethodsClonidine (30, 100, and 300 microg/g) was prepared in a cream base. In rat models of neuropathic pain, inflammatory pain, and postoperative pain, the authors evaluated effects of CC (0.1 g), topically applied onto the plantar surface of the injured or uninjured paw, on thermal hyperalgesia and mechanical allodynia to von Frey filaments. The authors also evaluated effects of CC on lumbar spinal Fos-like immunoreactivity.ResultsIn neuropathic rats, CC applied onto the injured paw reduced thermal hyperalgesia and mechanical allodynia dose dependently, whereas CC applied onto the uninjured paw had no effect. The antihypersensitivity effects of CC were antagonized by intraperitoneal yohimbine (10 mg/kg). Further, CC reduced Fos-like immunoreactivity in neuropathic rats. In contrast, CC in a single dose had no effects on hyperalgesia, allodynia, or Fos-like immunoreactivity in rats with inflammatory or postoperative pain. In rats with postoperative pain, CC repeatedly applied for 6 days reduced thermal hyperalgesia, but not mechanical allodynia, in the postoperative days, whereas it had no effects on hyperalgesia or allodynia in those with inflammatory pain.ConclusionsTopical CC in concentrations examined significantly reduced hypersensitivity and lumbar spinal Fos-like immunoreactivity in rats with neuropathic pain, probably through activation of peripherally located alpha2 adrenoceptors. However, CC was only partially effective and totally ineffective in rats with postoperative pain and inflammatory pain, respectively.

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