Volume 27, Issue 1 (March 2023)                   Physiol Pharmacol 2023, 27(1): 34-41 | Back to browse issues page

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Abbaszadeh F, Afhami M, Saghaei E, Naseri K, Hassanpour-ezatti M, Jorjani M. Sex influences on sensory responses followingspinothalamic tract injury in rats. Physiol Pharmacol 2023; 27 (1) :34-41
URL: http://ppj.phypha.ir/article-1-1843-en.html
Abstract:   (1057 Views)
Introduction: There is some evidence of significant differences in the recovery after spinal cord injury (SCI) between males and females. In this study, we investigated the sensory function and involvement of astrocytes in the sex differences of central pain syndrome in the unilateral spinothalamic tract (STT) injury model in rats.
Methods: Rats were divided into two groups: SCI and Sham groups received a unilateral electrolytic lesion on STT at T8-T9 and a control sham surgery respectively. After recovery from surgery, the sensory function was monitored for 28 days using tail flick and von Frey filament tests. The glial fibrillary acidic protein (GFAP) level was also measured by Western blot at the same time points.
Results: Mechanical hypersensitivity was increased from days 3 to 28 post-injury in male rats (P<0.001), but no significant change was observed in females. In the tail flick model, male rats had significantly elevated thermal withdrawal latency on day3 after STT lesion, while females showed a reduction in latency (P<0.001). Sex differences in GFAP level were observed during 4 weeks of study after injury. Results in the first week showed that GFAP level decreased in females, but the marked elevation was observed from days 7 to 28 in males (P<0.05).
Conclusion: This study revealed the sex differences in sensory dysfunction and the related astrocyte reactivity after SCI. It suggests a need for more studies using both sexes to fully explore the influence of sex on the recovery of sensory impairments post-SCI.
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Type of Manuscript: Experimental research article | Subject: Others

1. Acaz-Fonseca E, Sanchez-Gonzalez R, Azcoitia I, Arevalo MA, Garcia-Segura LM. Role of astrocytes in the neuroprotective actions of 17β-estradiol and selective estrogen receptor modulators. Mol Cell Endocrinol 2014; 389: 48-57. [DOI:10.1016/j.mce.2014.01.009]
2. Arevalo M-A, Santos-Galindo M, Bellini M-J, Azcoitia I, Garcia-Segura L M. Actions of estrogens on glial cells: implications for neuroprotection. Biochim Biophys Acta Gen Subj 2010; 1800: 1106-12. [DOI:10.1016/j.bbagen.2009.10.002]
3. Bartley E, Fillingim R. Sex differences in pain: A brief review of clinical and experimental findings. Surv Anesthesiol 2016; 60: 175-6. [DOI:10.1097/01.sa.0000484819.20819.8b]
4. Bartley EJ, Fillingim RB. Sex differences in pain: a brief review of clinical and experimental findings. Br J Anaesth 2013; 111: 52-8. [DOI:10.1093/bja/aet127]
5. Chambel SS, Tavares I, Cruz CD. Chronic Pain After Spinal Cord Injury: Is There a Role for Neuron-Immune Dysregulation? Front Physiol 2020; 11: 748.
6. Detloff MR, Fisher LC, McGaughy V, Longbrake EE, Popovich PG, Basso DM. Remote activation of microglia and pro-inflammatory cytokines predict the onset and severity of below-level neuropathic pain after spinal cord injury in rats. Exp Neurol 2008; 212: 337-47. [DOI:10.1016/j.expneurol.2008.04.009]
7. Fillingim RB, King CD, Ribeiro-Dasilva MC, Rahim-Williams B, Riley III JL. Sex, gender, and pain: a review of recent clinical and experimental findings. J Pain 2009; 10: 447-85. [DOI:10.1016/j.jpain.2008.12.001]
8. Gao Y-J, Ji R-R. Targeting astrocyte signaling for chronic pain. Neurotherapeutics 2010; 7: 482-93. [DOI:10.1016/j.nurt.2010.05.016]
9. Gaudet AD, Ayala MT, Schleicher WE, Smith EJ, Bateman EM, Maier SF, et al. Exploring acute-to-chronic neuropathic pain in rats after contusion spinal cord injury. Exp Neurol 2017; 295: 46-54. [DOI:10.1016/j.expneurol.2017.05.011]
10. Gaudet AD, Fonken LK. Glial cells shape pathology and repair after spinal cord injury. Neurotherapeutics 2018; 15: 554-77. [DOI:10.1007/s13311-018-0630-7]
11. Gupta DS, Hubscher CH. Estradiol treatment prevents injury induced enhancement in spinal cord dynorphin expression. Front Physiol 2012; 3: 28.
12. Hadjimarkou MM, Vasudevan N. GPER1/GPR30 in the brain: Crosstalk with classical estrogen receptors and implications for behavior. J Steroid Biochem Mol 2018; 176: 57-64. [DOI:10.1016/j.jsbmb.2017.04.012]
13. Hains BC, Waxman SG. Activated microglia contribute to the maintenance of chronic pain after spinal cord injury. J Neurosci 2006; 26: 4308-17. [DOI:10.1523/JNEUROSCI.0003-06.2006]
14. Hains BC, Yucra JA, Hulsebosch CE. Reduction of pathological and behavioral deficits following spinal cord contusion injury with the selective cyclooxygenase-2 inhibitor NS-398. J Neurotrauma 2001; 18: 409-23. [DOI:10.1089/089771501750170994]
15. Hulsebosch CE, Hains BC, Crown ED, Carlton SM. Mechanisms of chronic central neuropathic pain after spinal cord injury. Brain Res Rev 2009; 60: 202-13. [DOI:10.1016/j.brainresrev.2008.12.010]
16. Ji R-R, Donnelly CR, Nedergaard M. Astrocytes in chronic pain and itch. Nat Rev Neurosci 2019; 20: 667-85. [DOI:10.1038/s41583-019-0218-1]
17. Kawasaki Y, Zhang L, Cheng J-K, Ji R-R. Cytokine mechanisms of central sensitization: distinct and overlapping role of interleukin-1β, interleukin-6, and tumor necrosis factor-α in regulating synaptic and neuronal activity in the superficial spinal cord. J Neurosci 2008; 28: 5189-94. [DOI:10.1523/JNEUROSCI.3338-07.2008]
18. Kim HW, Won CH, Oh SB. Lack of correlation between spinal microgliosis and long-term development of tactile hypersensitivity in two different sciatic nerve crush injury. Mol Pain 2021; 17: 17448069211011326. [DOI:10.1177/17448069211011326]
19. Kuo J, Hamid N, Bondar G, Dewing P, Clarkson J, Micevych P. Sex differences in hypothalamic astrocyte response to estradiol stimulation. Biol Sex Differ 2010; 1: 7. [DOI:10.1186/2042-6410-1-7]
20. Mousavi Z, Shafaghi B, Kobarfard F, Jorjani M. Sex differences and role of gonadal hormones on glutamate level in the nucleus accumbens in morphine tolerant rats: a microdialysis study. Eur J Pharmacol 2007; 554: 145-9. [DOI:10.1016/j.ejphar.2006.10.010]
21. Nag S, Mokha S S. Testosterone is essential for α2-adrenoceptor-induced antinociception in the trigeminal region of the male rat. Neurosci Lett 2009; 467: 48-52. [DOI:10.1016/j.neulet.2009.10.016]
22. Naseri K, Saghaei E, Abbaszadeh F, Afhami M, Haeri A, Rahimi F, et al. Role of microglia and astrocyte in central pain syndrome following electrolytic lesion at the spinothalamic tract in rats. J Mol Neurosci 2013; 49: 470-9. [DOI:10.1007/s12031-012-9840-3]
23. Naseri K, Saghaei E, Abbaszadeh F, Afhami M, Haeri A, Jorjani M. The effect of estradiol on astrogliosis related to central pain syndrome after spinal cord injury in male rat. 14th World Congress on Pain, Milan, Italy 2012.
24. Okada-Ogawa A, Suzuki I, Sessle BJ, Chiang C-Y, Salter MW, Dostrovsky JO, et al. Astroglia in medullary dorsal horn (trigeminal spinal subnucleus caudalis) are involved in trigeminal neuropathic pain mechanisms. J Neurosci 2009; 29: 11161-71. [DOI:10.1523/JNEUROSCI.3365-09.2009]
25. Oyinbo CA. Secondary injury mechanisms in traumatic spinal cord injury: a nugget of this multiply cascade. Acta Neurobiol Exp (Wars) 2011; 71: 281-99.
26. Parducz A, Hajszan T, Maclusky N, Hoyk Z, Csakvari E, Kurunczi A, et al. Synaptic remodeling induced by gonadal hormones: neuronal plasticity as a mediator of neuroendocrine and behavioral responses to steroids. Neuroscience 2006; 138: 977-85. [DOI:10.1016/j.neuroscience.2005.07.008]
27. Ren K. An improved method for assessing mechanical allodynia in the rat. Physiol Behav 1999; 67: 711-6. [DOI:10.1016/S0031-9384(99)00136-5]
28. Saghaei E, Abbaszadeh F, Naseri K, Ghorbanpoor S, Afhami M, Haeri A, et al. Estradiol attenuates spinal cord injury-induced pain by suppressing microglial activation in thalamic VPL nuclei of rats. Neurosci Res 2013; 75: 316-23. [DOI:10.1016/j.neures.2013.01.010]
29. Schreiber KL, Beitz AJ, Wilcox GL. Activation of spinal microglia in a murine model of peripheral inflammation-induced, long-lasting contralateral allodynia. Neurosci Lett 2008; 440: 63-7. [DOI:10.1016/j.neulet.2008.05.044]
30. Sengelaub DR, Han Q, Liu N-K, Maczuga MA, Szalavari V, Valencia SA, et al. Protective effects of estradiol and dihydrotestosterone following spinal cord injury. Journal of neurotrauma 2018; 35: 825-41. [DOI:10.1089/neu.2017.5329]
31. Shiao R, Lee-Kubli CA. Neuropathic pain after spinal cord injury: challenges and research perspectives. Neurotherapeutics 2018; 15: 635-53. [DOI:10.1007/s13311-018-0633-4]
32. Sipski M L, Jackson AB, Gómez-Marín O, Estores I, Stein A. Effects of gender on neurologic and functional recovery after spinal cord injury. Arch Phys Med Rehabil 2004; 85: 1826-36. [DOI:10.1016/j.apmr.2004.04.031]
33. Sorge RE, Mapplebeck JC, Rosen S, Beggs S, Taves S, Alexander JK, et al. Different immune cells mediate mechanical pain hypersensitivity in male and female mice. Nat Neurosci 2015; 18: 1081-3. [DOI:10.1038/nn.4053]
34. Sribnick EA, Wingrave JM, Matzelle DD, Wilford GG, Ray SK, Banik NL. Estrogen attenuated markers of inflammation and decreased lesion volume in acute spinal cord injury in rats. J Neurosci Res 2005; 82: 283-93. [DOI:10.1002/jnr.20622]
35. Tran AP, Warren PM, Silver J. The biology of regeneration failure and success after spinal cord injury. Physiol Rev 2018; 98: 881-917. [DOI:10.1152/physrev.00017.2017]
36. Traub RJ, Ji Y. Sex differences and hormonal modulation of deep tissue pain. Front Neuroendocrinol 2013; 34: 350-66. [DOI:10.1016/j.yfrne.2013.07.002]
37. Wang G, Thompson SM. Maladaptive homeostatic plasticity in a rodent model of central pain syndrome: thalamic hyperexcitability after spinothalamic tract lesions. J Neurosci 2008; 28: 11959-69. [DOI:10.1523/JNEUROSCI.3296-08.2008]
38. Watson JL, Hala TJ, Putatunda R, Sannie D, Lepore AC. Persistent at-level thermal hyperalgesia and tactile allodynia accompany chronic neuronal and astrocyte activation in superficial dorsal horn following mouse cervical contusion spinal cord injury. PLoS One 2014; 9: e109099.
39. Yezierski RP. Pain following spinal cord injury: pathophysiology and central mechanisms. Prog Brain Res Vol 129: Elsevier, 2000: 429-49.

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