Analgesic effect of minocycline in rat model of inflammation-induced visceral pain.
The present study investigates the analgesic effect of minocycline, a semi-synthetic tetracycline antibiotic, in a rat model of inflammation-induced visceral pain. Inflammation was induced in male rats by intracolonic administration of tri-nitrobenzenesulphonic acid (TNBS). Visceral hyperalgesia was assessed by comparing the viscero-motor response (VMR) to graded colorectal distension (CRD) prior and post 7 days after TNBS treatment. Electrophysiology recordings from CRD-sensitive pelvic nerve afferents (PNA) and lumbo-sacral (LS) spinal neurons were performed in naïve and inflamed rats. Colonic inflammation produced visceral hyperalgesia characterized by increase in the VMRs to CRD accompanied with simultaneous activation of microglia in the spinal cord and satellite glial cells (SGCs) in the dorsal root ganglions (DRGs). Selectively inhibiting the glial activation following inflammation by araC (Arabinofuranosyl Cytidine) prevented the development of visceral hyperalgesia. Intrathecal minocycline significantly attenuated the VMR to CRD in inflamed rats, whereas systemic minocycline produced a delayed effect. In electrophysiology experiments, minocycline significantly attenuated the mechanotransduction of CRD-sensitive PNAs and the responses of CRD-sensitive LS spinal neurons in TNBS-treated rats. While the spinal effect of minocycline was observed within 5min of administration, systemic injection of the drug produced a delayed effect (60min) in inflamed rats. Interestingly, minocycline did not exhibit analgesic effect in naïve, non-inflamed rats. The results demonstrate that intrathecal injection of minocycline can effectively attenuate inflammation-induced visceral hyperalgesia. Minocycline might as well act on neuronal targets in the spinal cord of inflamed rats, in addition to the widely reported glial inhibitory action to produce analgesia.
Division of Gastroenterology and Hepatology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA.
Pradeep
P
Kannampalli
Division of Gastroenterology and Hepatology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA.
Soumya
S
Pochiraju
Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI, USA.
Mitchell
M
Bruckert
Division of Gastroenterology and Hepatology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA.
Reza
R
Shaker
Division of Gastroenterology and Hepatology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA.
Banani
B
Banerjee
Division of Gastroenterology and Hepatology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA; Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI, USA. Electronic address: sengupta@mcw.edu.
Jyoti N
JN
Sengupta
D000700:Analgesics / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D003106:Colon / Q000294:innervation*; D004195:Disease Models, Animal; D005727:Ganglia, Spinal / Q000187:drug effects / Q000503:physiopathology; D006930:Hyperalgesia / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control*; D007274:Injections, Intraperitoneal; D007278:Injections, Spinal; D008297:Male; D040542:Mechanotransduction, Cellular / Q000187:drug effects; D017628:Microglia / Q000187:drug effects; D008911:Minocycline / Q000008:administration & dosage / Q000494:pharmacology*; D058748:Pain Perception / Q000187:drug effects; D011312:Pressure; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000187:drug effects* / Q000503:physiopathology; D013997:Time Factors; D014302:Trinitrobenzenesulfonic Acid; D059265:Visceral Pain / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control*
D000700:Analgesics; D014302:Trinitrobenzenesulfonic Acid; D008911:Minocycline
Microglia; Minocycline; Satellite glial cell; TNBS; Visceral pain