Premium
Analgesic effects of serotonin and norepinephrine reuptake inhibitors on cold allodynia in rat chronic constriction injury model
Author(s) -
Hu DongQing,
Saclolo Eliza,
Burbach Leah,
Nunn Philip A,
Ford Anthony PDW,
Zhu QuanMing
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a683-c
Subject(s) - reboxetine , chemistry , pharmacology , reuptake , serotonin , reuptake inhibitor , bupropion , anesthesia , fluoxetine , yohimbine , allodynia , medicine , hyperalgesia , nociception , biochemistry , receptor , smoking cessation , pathology , antagonist
Serotonin (S) and norepinephrine (NE) have been implicated as mediators of endogenous analgesic mechanisms in the descending pain pathways. We investigated the effects of dual S and NE reuptake inhibitors (SNRI) duoxetine and velafaxine, selective SRI fluoxetine, NRI reboxetine and dopamine DRI bupropion on the cold allodynia induced by cold bath as well as by acetone in rat chronic constriction injury model (CCI). The right sciatic nerve of rats was barely loosed tied with four ligatures. Rats were used 1–4 weeks post CCI. For cold bath assay, each rat was placed on a metal plate in cold water (2–3°C) with the level of 1.5–2 cm above the plate. The injured‐paw lifts (out off water) within 1 min were recorded. For acetone assay, 0.2 ml acetone was applied onto the plantar paw. The withdraw latency was recorded. Duloxetine (1–30 mg/kg sc) dose‐dependently inhibited the cold allodynia with a 59±17.5% inhibition (p<0.05/<0.01 n=6–13) up to 3 h post dose. Venlafaxine (30 mg/kg sc), reboxetine (10 mg/kg sc), and fluoxetine (30 mg/kg po), but not bupropion (100 mg/kg po) produced significant inhibition in cold bath, and the inhibition rates (%) were 40.3±9.1, 61.±14.7 and 33.5±12.6, respectively (p<0.05 n=7–13). Morphine exhibited 64.3±13.4% inhibition (p<0.01 n=7). Similar results with duloxetine and reboxetine were obtained in acetone‐induced cold allodynia, however, fluoxetine and bupropion did not show significant effect in acetone assay. These results indicate that SNRI, NRI and SSRI, but not DRI exhibited analgesic effect on cold allodynia in CCI rats and that NE in particular as well as serotonin plays an important role in the inhibitory pathways of pain.