title: Efficacy of drugs with different mechanisms of action in relieving spontaneous pain at rest and during movement in a rat model of osteoarthritis.
abstract: Patients with osteoarthritis (OA) suffer from joint pain aggravated by movement, which affect their quality of life. In the present study, a weight bearing paradigm for pain at rest and a gait paradigm for pain during movement were tested in rats with unilateral knee arthritis induced by an intra-articular injection of sodium monoiodoacetate (MIA). At week 3 after MIA (1mg/knee) injection, animals developed pain-associated, right-left imbalances of weight distribution (weight bearing) or foot print parameters (gait). Diclofenac, at doses up to 30 mg/kg orally (p.o.), did not have a significant effect on either paradigm. Morphine rectified the weight bearing and gait imbalances at 1 and 3mg/kg subcutaneously, respectively. The weak opioid and serotonin/norepinephrine reuptake inhibitor (SNRI) tramadol also significantly corrected the indices at 10mg/kg (weight bearing) and 100mg/kg p.o. (gait). The SNRI duloxetine at 30 mg/kg p.o. corrected the weight bearing imbalance but not gait imbalance. We assessed the effect of different drugs on pain-induced disturbances in weight distribution and gait in MIA-induced arthritic rats. Analgesic drugs, each with different mechanisms of action, were less effective in rectifying the imbalance in gait than that in weight distribution. The assessment of the effect of analgesics on not only rest pain but pain during movement is valuable for the comprehensive examination of their therapeutic efficacies in OA.
authors.affiliation: Drug Discovery Research, Astellas Pharma Inc., 21 Miyukigaoka, Tsukuba, Ibaraki 305-8585, Japan. Electronic address: go.ishikawa@astellas.com.
authors.forename: Go
authors.initials: G
authors.lastname: Ishikawa
authors.affiliation: Drug Discovery Research, Astellas Pharma Inc., 21 Miyukigaoka, Tsukuba, Ibaraki 305-8585, Japan. Electronic address: yukinori.nagakura@astellas.com.
authors.forename: Yukinori
authors.initials: Y
authors.lastname: Nagakura
authors.affiliation: Drug Discovery Research, Astellas Pharma Inc., 21 Miyukigaoka, Tsukuba, Ibaraki 305-8585, Japan. Electronic address: nobuaki.takeshita@astellas.com.
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Takeshita
authors.affiliation: Drug Discovery Research, Astellas Pharma Inc., 21 Miyukigaoka, Tsukuba, Ibaraki 305-8585, Japan. Electronic address: yasuaki.shimizu@astellas.com.
authors.forename: Yasuaki
authors.initials: Y
authors.lastname: Shimizu
mesh_terms: D000779:Anesthetics, Local / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology / Q000627:therapeutic use; D004195:Disease Models, Animal; D000068736:Duloxetine Hydrochloride; D005684:Gait / Q000187:drug effects; D019807:Iodoacetic Acid / Q000009:adverse effects; D008297:Male; D009020:Morphine / Q000494:pharmacology / Q000627:therapeutic use; D009068:Movement / Q000187:drug effects*; D010003:Osteoarthritis / Q000139:chemically induced / Q000150:complications*; D010146:Pain / Q000150:complications* / Q000188:drug therapy* / Q000503:physiopathology; D051381:Rats; D012146:Rest; D013876:Thiophenes / Q000494:pharmacology / Q000627:therapeutic use; D014147:Tramadol / Q000494:pharmacology / Q000627:therapeutic use; D016474:Weight-Bearing / Q000502:physiology
chemical_list: D000779:Anesthetics, Local; D000894:Anti-Inflammatory Agents, Non-Steroidal; D013876:Thiophenes; D014147:Tramadol; D009020:Morphine; D000068736:Duloxetine Hydrochloride; D019807:Iodoacetic Acid
keywords: Analgesic; Diclofenac sodium (PubChem CID: 5018304); Duloxetine (PubChem CID: 60835); Lidocaine hydrochloride (PubChem CID: 6314); Morphine hydrochloride (PubChem CID: 5464110); Movement; Osteoarthritis; Pain; Rest; Spontaneous; Tramadol hydrochloride (PubChem CID: 63013)