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Persistent mechanical allodynia positively correlates with an increase in activated microglia and increased P-p38 mitogen-activated protein kinase activation in streptozotocin-induced diabetic rats.
Eur J Pain. 2014 Feb; 18(2):162-73.EJ

Abstract

BACKGROUND

In experimental early painful diabetic neuropathy, persistent hyperglycaemia induces dys-regulated sodium channel (Navs) expression in the dorsal root ganglion (DRG) and activates microglia in the spinal dorsal horn (SDH). However, information on diabetes-induced chronic neuropathic pain is limited. Therefore, we investigated abnormal Navs in the DRG and activated glial cells in the SDH of diabetic rats with chronic neuropathic pain.

METHODS

Sixty-six rats were divided into diabetic and control groups: control rats (n = 18; 1 mL of normal saline via the right femoral vein) and diabetic rats [n = 48; 60 mg/kg streptozotocin (STZ) via the right femoral vein]. Hindpaw behavioural tests, Navs expression in the DRG, activation of glial cells in the SDH and the number of neurons in the SDH were measured at 1 and 2 weeks, and 1, 2, 3 and 6 months following saline and STZ administration.

RESULTS

All diabetic rats exhibited hyperglycaemia from day 7 to 6 months. The diabetic rats decreased withdrawal threshold to mechanical stimuli but had blunted responses to thermal stimuli. Consistent up-regulation of Nav1.3 and down-regulation of Nav1.8 was observed. Microglial cells were activated early in the SDH and lasted for 6 months. A positive correlation between mechanical allodynia, Nav1.3 and microglial activation was observed. In addition, microglia activation in the SDH of STZ-induced diabetes was mediated, in part, by phosphorylation of p-38 mitogen-activated protein kinase.

CONCLUSIONS

Diabetic rats showed hindpaw mechanical allodynia for 6 months. Persistent mechanical allodynia was positively associated with sustained increased activation of Nav1.3 and increased p38 phosphorylation in activated microglia.

Authors+Show Affiliations

Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Taiwan; Department of Anesthesiology, Kaohsiung Medical University Hospital, Taiwan.No 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

23868758

Citation

Cheng, K-I, et al. "Persistent Mechanical Allodynia Positively Correlates With an Increase in Activated Microglia and Increased P-p38 Mitogen-activated Protein Kinase Activation in Streptozotocin-induced Diabetic Rats." European Journal of Pain (London, England), vol. 18, no. 2, 2014, pp. 162-73.
Cheng KI, Wang HC, Chuang YT, et al. Persistent mechanical allodynia positively correlates with an increase in activated microglia and increased P-p38 mitogen-activated protein kinase activation in streptozotocin-induced diabetic rats. Eur J Pain. 2014;18(2):162-73.
Cheng, K. I., Wang, H. C., Chuang, Y. T., Chou, C. W., Tu, H. P., Yu, Y. C., Chang, L. L., & Lai, C. S. (2014). Persistent mechanical allodynia positively correlates with an increase in activated microglia and increased P-p38 mitogen-activated protein kinase activation in streptozotocin-induced diabetic rats. European Journal of Pain (London, England), 18(2), 162-73. https://doi.org/10.1002/j.1532-2149.2013.00356.x
Cheng KI, et al. Persistent Mechanical Allodynia Positively Correlates With an Increase in Activated Microglia and Increased P-p38 Mitogen-activated Protein Kinase Activation in Streptozotocin-induced Diabetic Rats. Eur J Pain. 2014;18(2):162-73. PubMed PMID: 23868758.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Persistent mechanical allodynia positively correlates with an increase in activated microglia and increased P-p38 mitogen-activated protein kinase activation in streptozotocin-induced diabetic rats. AU - Cheng,K-I, AU - Wang,H-C, AU - Chuang,Y-T, AU - Chou,C-W, AU - Tu,H-P, AU - Yu,Y-C, AU - Chang,L-L, AU - Lai,C-S, Y1 - 2013/07/19/ PY - 2013/06/04/accepted PY - 2013/7/23/entrez PY - 2013/7/23/pubmed PY - 2014/9/5/medline SP - 162 EP - 73 JF - European journal of pain (London, England) JO - Eur J Pain VL - 18 IS - 2 N2 - BACKGROUND: In experimental early painful diabetic neuropathy, persistent hyperglycaemia induces dys-regulated sodium channel (Navs) expression in the dorsal root ganglion (DRG) and activates microglia in the spinal dorsal horn (SDH). However, information on diabetes-induced chronic neuropathic pain is limited. Therefore, we investigated abnormal Navs in the DRG and activated glial cells in the SDH of diabetic rats with chronic neuropathic pain. METHODS: Sixty-six rats were divided into diabetic and control groups: control rats (n = 18; 1 mL of normal saline via the right femoral vein) and diabetic rats [n = 48; 60 mg/kg streptozotocin (STZ) via the right femoral vein]. Hindpaw behavioural tests, Navs expression in the DRG, activation of glial cells in the SDH and the number of neurons in the SDH were measured at 1 and 2 weeks, and 1, 2, 3 and 6 months following saline and STZ administration. RESULTS: All diabetic rats exhibited hyperglycaemia from day 7 to 6 months. The diabetic rats decreased withdrawal threshold to mechanical stimuli but had blunted responses to thermal stimuli. Consistent up-regulation of Nav1.3 and down-regulation of Nav1.8 was observed. Microglial cells were activated early in the SDH and lasted for 6 months. A positive correlation between mechanical allodynia, Nav1.3 and microglial activation was observed. In addition, microglia activation in the SDH of STZ-induced diabetes was mediated, in part, by phosphorylation of p-38 mitogen-activated protein kinase. CONCLUSIONS: Diabetic rats showed hindpaw mechanical allodynia for 6 months. Persistent mechanical allodynia was positively associated with sustained increased activation of Nav1.3 and increased p38 phosphorylation in activated microglia. SN - 1532-2149 UR - https://www.unboundmedicine.com/medline/citation/23868758/Persistent_mechanical_allodynia_positively_correlates_with_an_increase_in_activated_microglia_and_increased_P_p38_mitogen_activated_protein_kinase_activation_in_streptozotocin_induced_diabetic_rats_ L2 - https://doi.org/10.1002/j.1532-2149.2013.00356.x DB - PRIME DP - Unbound Medicine ER -