Meta-chlorophenylpiperazine attenuates formalin-induced nociceptive responses through 5-HT1/2 receptors in both normal and diabetic mice.
1. This study was designed to investigate the effect of meta-chlorophenylpiperazine (m-CPP; a 5-hydroxytryptamine (5-HT) receptor agonist) on the formalin-induced nociceptive responses in normal, insulin-dependent streptozotocin (STZ) diabetic and non-insulin dependent genetically diabetic (db/db) mice. 2. A subcutaneous injection of diluted formalin (1% formaldehyde in 0.9% saline, 10 microliters) under the plantar surface of the left hindpaw induced biphasic nociceptive responses, the first and second phases considered to represent acute and chronic pain, respectively. The former response in db/db mice was significantly lower than those in normal mice, and the latter responses in STZ and db/db mice were significantly lower than those in normal mice. 3. In normal mice, m-CPP (0.32-3.2 mg ml-1, p.o.) exhibited potent antinociceptive activity, dose-dependently attenuating the first and second phase; the ID50 value of the second phase was 0.4 mg kg-1. m-CPP (0.32-3.2 mg kg-1, p.o.) also dose-dependently attenuated the formalin-induced nociceptive responses in STZ-induced diabetic mice and genetically diabetic db/db mice, and the activities were comparable to those in normal mice. 4. The antinociceptive activities of m-CPP (1 mg kg-1, p.o.) were significantly inhibited by pretreatment with pindolol (a 5-HT1-receptor antagonist, 1 mg kg-1, i.p.) or ketanserin (a 5-HT2 receptor antagonist, 1 mg kg-1, i.p.) but were hardly affected by ICS205-930 (a 5-HT3 receptor antagonist, 1 mg kg-1, i.p.). 5. These results suggest that m-CPP inhibits not only acute but also chronic pain transmission through 5-HT1 and 5-HT2 receptors, and that the 5-hydroxytryptaminergic antinociceptive pathways are little affected by diabetes.
Takeshita
N
N
Tsukuba Research Laboratories, Fujisawa Pharmaceutical Co. Ltd., Ibaraki, Japan.
Yamaguchi
I
I
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology*; D005557:Formaldehyde; D007211:Indoles / Q000494:pharmacology; D007650:Ketanserin / Q000494:pharmacology; D008297:Male; D051379:Mice; D010147:Pain Measurement / Q000187:drug effects*; D010879:Piperazines / Q000494:pharmacology*; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D000077526:Tropisetron
D007211:Indoles; D010879:Piperazines; D011985:Receptors, Serotonin; D017366:Serotonin Receptor Agonists; D005557:Formaldehyde; D000077526:Tropisetron; D007650:Ketanserin; C015068:1-(3-chlorophenyl)piperazine