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Gabapentin reverses microglial activation in the spinal cord of streptozotocin-induced diabetic rats.
Eur J Pain. 2009 Sep; 13(8):807-11.EJ

Abstract

Diabetes mellitus is the leading cause of peripheral neuropathy worldwide. Despite this high level of incidence, underlying mechanisms of the development and maintenance of neuropathic pain are still poorly understood. Evidence supports a prominent role of glial cells in neuropathic pain states. Gabapentin is used clinically and shows some efficacy in the treatment of neuropathic pain. Here we investigate the distribution and activation of spinal microglia and astrocytes in streptozotocin (STZ)-diabetic rats and the effect of the gold standard analgesic, Gabapentin, on these cells. Mechanical allodynia was observed in four week-diabetic rats. Oral administration of Gabapentin significantly attenuated mechanical allodynia. Quantification of cell markers Iba-1 for microglia and GFAP for astrocytes revealed extensive activation of microglia in the dorsal horn of diabetic rats, whereas a reduction in the number of astrocytes could be observed. In addition, an attenuation of microglial activation correlated with reduced allodynia following Gabapentin treatment, while Gabapentin had no effect on the number of astrocytes. Here we show a role of microglia in STZ-induced mechanical allodynia and furthermore, that the anti-allodynic effect of Gabapentin may be linked to a reduction of spinal microglial activation. Astrocytic activation in this model appears to be limited and is unaffected by Gabapentin treatment. Consequently, spinal microglial activation is a key mechanism underlying diabetic neuropathy. Furthermore, we suggest that Gabapentin may exert its anti-allodynic actions partially through alterations of microglial cell function.

Authors+Show Affiliations

Neurorestoration Group, Wolfson Centre for Age Related Diseases, King's College London, London SE1 1UL, UK.No 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

18977160

Citation

Wodarski, Rachel, et al. "Gabapentin Reverses Microglial Activation in the Spinal Cord of Streptozotocin-induced Diabetic Rats." European Journal of Pain (London, England), vol. 13, no. 8, 2009, pp. 807-11.
Wodarski R, Clark AK, Grist J, et al. Gabapentin reverses microglial activation in the spinal cord of streptozotocin-induced diabetic rats. Eur J Pain. 2009;13(8):807-11.
Wodarski, R., Clark, A. K., Grist, J., Marchand, F., & Malcangio, M. (2009). Gabapentin reverses microglial activation in the spinal cord of streptozotocin-induced diabetic rats. European Journal of Pain (London, England), 13(8), 807-11. https://doi.org/10.1016/j.ejpain.2008.09.010
Wodarski R, et al. Gabapentin Reverses Microglial Activation in the Spinal Cord of Streptozotocin-induced Diabetic Rats. Eur J Pain. 2009;13(8):807-11. PubMed PMID: 18977160.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Gabapentin reverses microglial activation in the spinal cord of streptozotocin-induced diabetic rats. AU - Wodarski,Rachel, AU - Clark,Anna K, AU - Grist,John, AU - Marchand,Fabien, AU - Malcangio,Marzia, Y1 - 2008/10/31/ PY - 2008/06/24/received PY - 2008/08/11/revised PY - 2008/09/18/accepted PY - 2008/11/4/pubmed PY - 2009/10/24/medline PY - 2008/11/4/entrez SP - 807 EP - 11 JF - European journal of pain (London, England) JO - Eur J Pain VL - 13 IS - 8 N2 - Diabetes mellitus is the leading cause of peripheral neuropathy worldwide. Despite this high level of incidence, underlying mechanisms of the development and maintenance of neuropathic pain are still poorly understood. Evidence supports a prominent role of glial cells in neuropathic pain states. Gabapentin is used clinically and shows some efficacy in the treatment of neuropathic pain. Here we investigate the distribution and activation of spinal microglia and astrocytes in streptozotocin (STZ)-diabetic rats and the effect of the gold standard analgesic, Gabapentin, on these cells. Mechanical allodynia was observed in four week-diabetic rats. Oral administration of Gabapentin significantly attenuated mechanical allodynia. Quantification of cell markers Iba-1 for microglia and GFAP for astrocytes revealed extensive activation of microglia in the dorsal horn of diabetic rats, whereas a reduction in the number of astrocytes could be observed. In addition, an attenuation of microglial activation correlated with reduced allodynia following Gabapentin treatment, while Gabapentin had no effect on the number of astrocytes. Here we show a role of microglia in STZ-induced mechanical allodynia and furthermore, that the anti-allodynic effect of Gabapentin may be linked to a reduction of spinal microglial activation. Astrocytic activation in this model appears to be limited and is unaffected by Gabapentin treatment. Consequently, spinal microglial activation is a key mechanism underlying diabetic neuropathy. Furthermore, we suggest that Gabapentin may exert its anti-allodynic actions partially through alterations of microglial cell function. SN - 1532-2149 UR - https://www.unboundmedicine.com/medline/citation/18977160/Gabapentin_reverses_microglial_activation_in_the_spinal_cord_of_streptozotocin_induced_diabetic_rats_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1090-3801(08)00205-X DB - PRIME DP - Unbound Medicine ER -