Analgesic Effect of Minocycline in Rat Model of Inflammation-induced Visceral Pain

Overview

Journal Eur J Pharmacol

Specialty Pharmacology

Date 2014 Feb 4

PMID 24485889

Citations 12

Authors

Pradeep Kannampalli

Soumya Pochiraju

Mitchell Bruckert

Reza Shaker

Banani Banerjee

Jyoti N Sengupta

Affiliations

Soon will be listed here.

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.

Citing Articles

Differential Regulation of Intracisternally Injected Angiotensin II-Induced Mechanical Allodynia and Thermal Hyperalgesia in Rats.

Park K, Son J, Kim H, Kim Y, Ju J, Jo M Biomedicines. 2023; 11(12).

PMID: 38137500 PMC: 10741042. DOI: 10.3390/biomedicines11123279.

Minocycline synergizes with corticosteroids in reducing colitis severity in mice via the modulation of pro-inflammatory molecules.

Khajah M, Hawai S, Barakat A, Albaloushi A, Alkharji M, Masocha W Front Pharmacol. 2023; 14:1252174.

PMID: 38034999 PMC: 10687282. DOI: 10.3389/fphar.2023.1252174.

Antimicrobial therapies for chronic pain (part 1): analgesic mechanisms.

Wang E, Karri J, Tontisirin N, Cohen S Korean J Pain. 2023; 36(3):281-298.

PMID: 37394272 PMC: 10322662. DOI: 10.3344/kjp.23129.

Inhibition of P2X7 receptors by Lu AF27139 diminishes colonic hypersensitivity and CNS prostanoid levels in a rat model of visceral pain.

Staal R, Gandhi A, Zhou H, Cajina M, Jacobsen A, Hestehave S Purinergic Signal. 2022; 18(4):499-514.

PMID: 36001278 PMC: 9832206. DOI: 10.1007/s11302-022-09892-0.

Experimental Infection Induces Pain in Mice Dependent on Early Spinal Cord Glial Cells and NFκB Activation and Cytokine Production.

Borghi S, Fattori V, Carvalho T, Tatakihara V, Zaninelli T, Pinho-Ribeiro F Front Immunol. 2021; 11:539086.

PMID: 33574810 PMC: 7870690. DOI: 10.3389/fimmu.2020.539086.

References

Jin S, Zhuang Z, Woolf C, Ji R . p38 mitogen-activated protein kinase is activated after a spinal nerve ligation in spinal cord microglia and dorsal root ganglion neurons and contributes to the generation of neuropathic pain. J Neurosci. 2003; 23(10):4017-22. PMC: 6741086. View

Hanani M . Satellite glial cells in sensory ganglia: from form to function. Brain Res Brain Res Rev. 2005; 48(3):457-76. DOI: 10.1016/j.brainresrev.2004.09.001. View

Cao H, Zhang Y . Spinal glial activation contributes to pathological pain states. Neurosci Biobehav Rev. 2008; 32(5):972-83. DOI: 10.1016/j.neubiorev.2008.03.009. View

Tikka T, Fiebich B, Goldsteins G, Keinanen R, Koistinaho J . Minocycline, a tetracycline derivative, is neuroprotective against excitotoxicity by inhibiting activation and proliferation of microglia. J Neurosci. 2001; 21(8):2580-8. PMC: 6762519. View

Kettenmann H, Hanisch U, Noda M, Verkhratsky A . Physiology of microglia. Physiol Rev. 2011; 91(2):461-553. DOI: 10.1152/physrev.00011.2010. View

Takeda M, Takahashi M, Matsumoto S . Contribution of the activation of satellite glia in sensory ganglia to pathological pain. Neurosci Biobehav Rev. 2009; 33(6):784-92. DOI: 10.1016/j.neubiorev.2008.12.005. View

Luo H, Cheng J, Han J, Wan Y . Change of vanilloid receptor 1 expression in dorsal root ganglion and spinal dorsal horn during inflammatory nociception induced by complete Freund's adjuvant in rats. Neuroreport. 2004; 15(4):655-8. DOI: 10.1097/00001756-200403220-00016. View

van der Kogel A, Sissingh H . Effects of intrathecal methotrexate and cytosine arabinoside on the radiation tolerance of the rat spinal cord. Radiother Oncol. 1985; 4(3):239-51. DOI: 10.1016/s0167-8140(85)80089-x. View

Thomas M, Le W . Minocycline: neuroprotective mechanisms in Parkinson's disease. Curr Pharm Des. 2004; 10(6):679-86. DOI: 10.2174/1381612043453162. View

10.

Stuesse S, Cruce W, Lovell J, McBurney D, CRISP T . Microglial proliferation in the spinal cord of aged rats with a sciatic nerve injury. Neurosci Lett. 2000; 287(2):121-4. DOI: 10.1016/s0304-3940(00)01142-3. View

11.

Scholz J, Abele A, Marian C, Haussler A, Herbert T, Woolf C . Low-dose methotrexate reduces peripheral nerve injury-evoked spinal microglial activation and neuropathic pain behavior in rats. Pain. 2008; 138(1):130-142. PMC: 2536692. DOI: 10.1016/j.pain.2007.11.019. View

12.

ARONSON A . Pharmacotherapeutics of the newer tetracyclines. J Am Vet Med Assoc. 1980; 176(10 Spec No):1061-8. View

13.

Suter M, Wen Y, Decosterd I, Ji R . Do glial cells control pain?. Neuron Glia Biol. 2008; 3(3):255-68. PMC: 2394739. DOI: 10.1017/S1740925X08000100. View

14.

Cho I, Lee M, Jang M, Gwak N, Lee K, Jung H . Minocycline markedly reduces acute visceral nociception via inhibiting neuronal ERK phosphorylation. Mol Pain. 2012; 8:13. PMC: 3342906. DOI: 10.1186/1744-8069-8-13. View

15.

Saura J . Microglial cells in astroglial cultures: a cautionary note. J Neuroinflammation. 2007; 4:26. PMC: 2140055. DOI: 10.1186/1742-2094-4-26. View

16.

DeLeo J, Yezierski R . The role of neuroinflammation and neuroimmune activation in persistent pain. Pain. 2001; 90(1-2):1-6. DOI: 10.1016/s0304-3959(00)00490-5. View

17.

Audet J, Gowing G, Paradis R, Soucy G, Julien J . Ablation of proliferating cells in the CNS exacerbates motor neuron disease caused by mutant superoxide dismutase. PLoS One. 2012; 7(4):e34932. PMC: 3327706. DOI: 10.1371/journal.pone.0034932. View

18.

Zhang H, Yoon S, Zhang H, Dougherty P . Evidence that spinal astrocytes but not microglia contribute to the pathogenesis of Paclitaxel-induced painful neuropathy. J Pain. 2012; 13(3):293-303. PMC: 3294066. DOI: 10.1016/j.jpain.2011.12.002. View

19.

Stirling D, Koochesfahani K, Steeves J, Tetzlaff W . Minocycline as a neuroprotective agent. Neuroscientist. 2005; 11(4):308-22. DOI: 10.1177/1073858405275175. View

20.

Lin C, Tsaur M, Chen C, Wang T, Lin C, Lai Y . Chronic intrathecal infusion of minocycline prevents the development of spinal-nerve ligation-induced pain in rats. Reg Anesth Pain Med. 2007; 32(3):209-16. DOI: 10.1016/j.rapm.2007.01.005. View