title: Spontaneous and evoked pain-associated behaviors in a rat model of neuropathic pain respond differently to drugs with different mechanisms of action.
abstract: Given that patients with neuropathic pain suffer a mixture of spontaneous and evoked pain symptoms, we assessed the effects of drugs with different mechanism of action on spontaneous and evoked pain-associated behaviors in a rat model of neuropathic pain induced by chronic constriction injury (CCI) of the sciatic nerve. Frequent aberrant limb movement on the operated side was measured to assess spontaneous pain-associated behavior, and mechanical allodynia and thermal hyperalgesia were evaluated to assess evoked pain-associated behaviors. These three types of behavior were assessed after administration of the following drugs: pregabalin (α2δ-subunit ligand), morphine (μ-opioid receptor agonist), perampanel (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid [AMPA] receptor antagonist), clonidine, dexmedetomidine (α2-adrenoceptor agonists), and diclofenac (non-steroidal anti-inflammatory drug [NSAID]). Pregabalin at an oral dose of 10 or 30mg/kg significantly alleviated frequent aberrant limb movement and mechanical allodynia, but not thermal hyperalgesia. Morphine at a subcutaneous dose of 1 or 3mg/kg significantly improved all three types of behavior. Perampanel at an oral dose of 1mg/kg attenuated only frequent aberrant limb movement. Intraperitoneal administration of clonidine (0.01 or 0.03mg/kg) and dexmedetomidine (0.03mg/kg) significantly improved all three types of behavior, while diclofenac did not relieve any of the behaviors. Pregabalin, clonidine, and dexmedetomidine significantly decreased motor performance at doses close to analgesic doses in the rotarod test. The present study demonstrates that responses to spontaneous and evoked pain symptoms in neuropathic pain condition differ depending on a drug's mechanism of action. The selection and application of drugs according to the specific symptoms would be considered for the medication of patients with neuropathic pain.
authors.affiliation: Drug Discovery Research, Astellas Pharma, Inc., 21 Miyukigaoka, Tsukuba, Ibaraki 305-8585, Japan. Electronic address: nobuhito.murai@astellas.com.
authors.forename: Nobuhito
authors.initials: N
authors.lastname: Murai
authors.affiliation: Drug Discovery Research, Astellas Pharma, Inc., 21 Miyukigaoka, Tsukuba, Ibaraki 305-8585, Japan.
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Sekizawa
authors.affiliation: Drug Discovery Research, Astellas Pharma, Inc., 21 Miyukigaoka, Tsukuba, Ibaraki 305-8585, Japan.
authors.forename: Takayasu
authors.initials: T
authors.lastname: Gotoh
authors.affiliation: Drug Discovery Research, Astellas Pharma, Inc., 21 Miyukigaoka, Tsukuba, Ibaraki 305-8585, Japan.
authors.forename: Tomonari
authors.initials: T
authors.lastname: Watabiki
authors.affiliation: Drug Discovery Research, Astellas Pharma, Inc., 21 Miyukigaoka, Tsukuba, Ibaraki 305-8585, Japan.
authors.forename: Masayasu
authors.initials: M
authors.lastname: Takahashi
authors.affiliation: Drug Discovery Research, Astellas Pharma, Inc., 21 Miyukigaoka, Tsukuba, Ibaraki 305-8585, Japan.
authors.forename: Shuichiro
authors.initials: S
authors.lastname: Kakimoto
authors.affiliation: Astellas Pharma Research Technologies Co., Ltd., 21 Miyukigaoka, Tsukuba, Ibaraki 305-8585, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Takahashi
authors.affiliation: Astellas Pharma Research Technologies Co., Ltd., 21 Miyukigaoka, Tsukuba, Ibaraki 305-8585, Japan.
authors.forename: Masanobu
authors.initials: M
authors.lastname: Iino
authors.affiliation: Drug Discovery Research, Astellas Pharma, Inc., 21 Miyukigaoka, Tsukuba, Ibaraki 305-8585, Japan.
authors.forename: Yukinori
authors.initials: Y
authors.lastname: Nagakura
mesh_terms: D000700:Analgesics / Q000627:therapeutic use*; D000818:Animals; D004195:Disease Models, Animal; D008297:Male; D009437:Neuralgia / Q000188:drug therapy* / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000700:Analgesics
keywords: Chronic constriction injury; Mechanical allodynia; Neuropathic pain; Spontaneous pain; Thermal hyperalgesia