Faculty Collaboration Database

Analgesic effect of minocycline in rat model of inflammation-induced visceral pain. Eur J Pharmacol 2014 Mar 15;727:87-98

Date

02/04/2014

Pubmed ID

24485889

Pubmed Central ID

PMC3984928

DOI

10.1016/j.ejphar.2014.01.026

Scopus ID

2-s2.0-84893705940 (requires institutional sign-in at Scopus site)   30 Citations

Abstract

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.

Author List

Kannampalli P, Pochiraju S, Bruckert M, Shaker R, Banerjee B, Sengupta JN

Authors

Banani Banerjee PhD Associate Professor in the Medicine department at Medical College of Wisconsin
Jyoti N. Sengupta PhD Professor in the Medicine department at Medical College of Wisconsin
Reza Shaker MD Assoc Provost, Sr Assoc Dean, Ctr Dir, Chief, Prof in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Analgesics
Animals
Behavior, Animal
Colitis
Colon
Disease Models, Animal
Ganglia, Spinal
Hyperalgesia
Injections, Intraperitoneal
Injections, Spinal
Male
Mechanotransduction, Cellular
Microglia
Minocycline
Pain Perception
Pressure
Rats, Sprague-Dawley
Spinal Cord
Time Factors
Trinitrobenzenesulfonic Acid
Visceral Pain