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Spinal microglia initiate and maintain hyperalgesia in a rat model of chronic pancreatitis.
Gastroenterology. 2012 Jan; 142(1):165-173.e2.G

Abstract

BACKGROUND & AIMS

The chronic, persistent pain associated with chronic pancreatitis (CP) has many characteristics of neuropathic pain, initiated and maintained by the activation of spinal microglia. We investigated whether activated microglia in the thoracic spinal cord contribute to chronic pain in a rat model of CP.

METHODS

CP was induced in Sprague-Dawley rats by an intraductal injection of 2% trinitrobenzene sulfonic acid. Hyperalgesia was assessed by the measurement of mechanical sensitivity of the abdomen and nocifensive behavior to electrical stimulation of the pancreas. Three weeks after induction of CP, spinal samples were analyzed by immunostaining and immunoblot analyses for levels of CD11 (a marker of microglia, determined with the antibody OX42) and phosphorylated p38 (P-p38, a marker of activation of p38 mitogen-activated protein kinase signaling). We examined the effects of minocycline (inhibitor of microglia) and fractalkine (microglia-activating factor) on visceral hyperalgesia in rats with CP.

RESULTS

Rats with CP had increased sensitivity and nociceptive behaviors to mechanical probing of the abdomen and electrical stimulation of the pancreas. The dorsal horn of the thoracic spinal cords of rats with CP contained activated microglia (based on increased staining with OX42), with an ameboid appearance. Levels of P-p38 increased in rats with CP and colocalized with OX42-positive cells. Intrathecal injection of minocycline reversed and prevented the increase of nocifensive behaviors and levels of P-p38 in rats with CP. Fractalkine induced hyperalgesia in rats without CP, which was blocked by minocycline.

CONCLUSIONS

Activated spinal microglia have important roles in maintaining and initiating chronic pain in a rat model of CP. Microglia might be a target for treatment of hyperalgesia caused by pancreatic inflammation.

Authors+Show Affiliations

Institute of Brain Science, National Yang-Ming University, Taipei, Taiwan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21963786

Citation

Liu, Pei-Yi, et al. "Spinal Microglia Initiate and Maintain Hyperalgesia in a Rat Model of Chronic Pancreatitis." Gastroenterology, vol. 142, no. 1, 2012, pp. 165-173.e2.
Liu PY, Lu CL, Wang CC, et al. Spinal microglia initiate and maintain hyperalgesia in a rat model of chronic pancreatitis. Gastroenterology. 2012;142(1):165-173.e2.
Liu, P. Y., Lu, C. L., Wang, C. C., Lee, I. H., Hsieh, J. C., Chen, C. C., Lee, H. F., Lin, H. C., Chang, F. Y., & Lee, S. D. (2012). Spinal microglia initiate and maintain hyperalgesia in a rat model of chronic pancreatitis. Gastroenterology, 142(1), 165-e2. https://doi.org/10.1053/j.gastro.2011.09.041
Liu PY, et al. Spinal Microglia Initiate and Maintain Hyperalgesia in a Rat Model of Chronic Pancreatitis. Gastroenterology. 2012;142(1):165-173.e2. PubMed PMID: 21963786.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Spinal microglia initiate and maintain hyperalgesia in a rat model of chronic pancreatitis. AU - Liu,Pei-Yi, AU - Lu,Ching-Liang, AU - Wang,Chia-Chuan, AU - Lee,I-Hui, AU - Hsieh,Jen-Chuen, AU - Chen,Chun-Chia, AU - Lee,Hsing-Feng, AU - Lin,Han-Chieh, AU - Chang,Full-Young, AU - Lee,Shou-Dong, Y1 - 2011/10/01/ PY - 2011/01/13/received PY - 2011/07/21/revised PY - 2011/09/20/accepted PY - 2011/10/4/entrez PY - 2011/10/4/pubmed PY - 2012/2/15/medline SP - 165 EP - 173.e2 JF - Gastroenterology JO - Gastroenterology VL - 142 IS - 1 N2 - BACKGROUND & AIMS: The chronic, persistent pain associated with chronic pancreatitis (CP) has many characteristics of neuropathic pain, initiated and maintained by the activation of spinal microglia. We investigated whether activated microglia in the thoracic spinal cord contribute to chronic pain in a rat model of CP. METHODS: CP was induced in Sprague-Dawley rats by an intraductal injection of 2% trinitrobenzene sulfonic acid. Hyperalgesia was assessed by the measurement of mechanical sensitivity of the abdomen and nocifensive behavior to electrical stimulation of the pancreas. Three weeks after induction of CP, spinal samples were analyzed by immunostaining and immunoblot analyses for levels of CD11 (a marker of microglia, determined with the antibody OX42) and phosphorylated p38 (P-p38, a marker of activation of p38 mitogen-activated protein kinase signaling). We examined the effects of minocycline (inhibitor of microglia) and fractalkine (microglia-activating factor) on visceral hyperalgesia in rats with CP. RESULTS: Rats with CP had increased sensitivity and nociceptive behaviors to mechanical probing of the abdomen and electrical stimulation of the pancreas. The dorsal horn of the thoracic spinal cords of rats with CP contained activated microglia (based on increased staining with OX42), with an ameboid appearance. Levels of P-p38 increased in rats with CP and colocalized with OX42-positive cells. Intrathecal injection of minocycline reversed and prevented the increase of nocifensive behaviors and levels of P-p38 in rats with CP. Fractalkine induced hyperalgesia in rats without CP, which was blocked by minocycline. CONCLUSIONS: Activated spinal microglia have important roles in maintaining and initiating chronic pain in a rat model of CP. Microglia might be a target for treatment of hyperalgesia caused by pancreatic inflammation. SN - 1528-0012 UR - https://www.unboundmedicine.com/medline/citation/21963786/Spinal_microglia_initiate_and_maintain_hyperalgesia_in_a_rat_model_of_chronic_pancreatitis_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0016-5085(11)01366-7 DB - PRIME DP - Unbound Medicine ER -