Skip to main content

Advertisement

Log in

Time-dependent photobiomodulation management of neuropathic pain induced by spinal cord injury in male rats

  • Original Article
  • Published:
Lasers in Medical Science Aims and scope Submit manuscript

Abstract

Neuropathic pain (NP) following spinal cord injury (SCI) often lasts for a long time and causes a range of problems that reduce the quality of life. Current treatments are not generally effective; however, photobiomodulation therapy (PBMT) has made some progress in this area. Due to the novelty of this treatment, standard therapeutic protocols have not yet been agreed upon. In the present study, we compare the analgesic effect of two PBMT protocols (2 and 4 weeks of radiation). A total of thirty-two adult male Wistar rats were divided into four groups: control, SCI, 2 W PBMT, and 4 W PBMT. SCI was induced by an aneurism clip and PBMT used a 660-nm, initiated 30 min post-SCI, and continued daily for 2 or 4 weeks. Functional recovery, hyperalgesia, and allodynia were measured weekly. At the end of the study, the Gad65, interleukin 1-alpha (IL1α), interleukin 10 (IL10), IL4, and purinergic receptor (P2xR and P2yR) expressions were measured. Data were analyzed by Prism6. The results showed PBM irradiation for 2 and 4 weeks had the same effects in improving hyperalgesia. In the case of allodynia and functional recovery, 4 W PBMT was more effective (p<0.01). 4 W PBMT increased the Gad65 expression (p <0.001) and reduced P2Y4R (p <0.05) compared to SCI animals. The effects of 2 and 4 W PBMT were the same for IL1α, IL10, and P2X3 receptors. 4 W PBMT was more effective in reducing the complications of SCI such as pain and disability. PBMT therapy is an effective method aimed at immune system function modulation to reduce NP and motor dysfunction.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

References

  1. Saffarpour S, Shaabani M, Naghdi N, Farahmandfar M, Janzadeh A, Nasirinezhad F (2017) In vivo evaluation of the hippocampal glutamate, GABA and the BDNF levels associated with spatial memory performance in a rodent model of neuropathic pain. Physiol Behav 175:97–103

    Article  CAS  PubMed  Google Scholar 

  2. Mojarad N, Janzadeh A, Yousefifard M, Nasirinezhad F (2018) The role of low level laser therapy on neuropathic pain relief and interleukin-6 expression following spinal cord injury: an experimental study. J Chem Neuroanat 87:60–70

    Article  CAS  PubMed  Google Scholar 

  3. Ramezani F, Farzad BR, Janzadeh A (2021) Personalized pain medicine: turning theory into Policy. Arch Neurosci 8:e116180

    Article  Google Scholar 

  4. Jameie SB, Shams-Hosseini NS, Janzadeh A, Sharifi M, Kerdari M (2012) Health related quality of life and pain characteristics among Iranian patients suffering non-malignant chronic pain. Med J Islam Repub Iran 26:118–124

    PubMed  PubMed Central  Google Scholar 

  5. Wu Y-T, Li T-Y, Chu H-Y, Chen L-C, Chiang S-L, Chang S-T (2011) Relationship between the interval before high-dose methylprednisolone administration and chronic pain in traumatic spinal cord injury. Neurosciences (Riyadh) 16:324–328

    PubMed  Google Scholar 

  6. Nasirinezhad F, Hosseini M, Karami Z, Yousefifard M, Janzadeh A (2016) Spinal 5-HT3 receptor mediates nociceptive effect on central neuropathic pain; possible therapeutic role for tropisetron. J Spinal Cord Med 39:212–219

    Article  PubMed  PubMed Central  Google Scholar 

  7. Gill LC, Gransee HM, Sieck GC, Mantilla CB (2016) Functional recovery after cervical spinal cord injury: role of neurotrophin and glutamatergic signaling in phrenic motoneurons. Respir Physiol Neurobiol 226:128–136

    Article  CAS  PubMed  Google Scholar 

  8. Lv R, Du L, Zhang L, Zhang Z (2019) Polydatin attenuates spinal cord injury in rats by inhibiting oxidative stress and microglia apoptosis via Nrf2/HO-1 pathway. Life Sci 217:119–127

    Article  CAS  PubMed  Google Scholar 

  9. An Y, Li J, Yuan Q, Fan M (2020) MicroRNA-466c-3p exerts protective effect on neuronal apoptosis and improves functional recovery post spinal cord injury via mitochondrial apoptotic pathway. AMB Express 10:113

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Zhang HW, Ding JD, Zhang ZS, Zhao S-S, Duan K-Y, Zhu B-Q, Zhao W-F, Chai Z-T, Liu X-W (2020) Critical role of p38 in spinal cord injury by regulating inflammation and apoptosis in a rat model. Spine (Phila Pa 1976) 45:E355–E363

    Article  PubMed  Google Scholar 

  11. Janzadeh A, Sarveazad A, Hamblin MR, Taheripak G, Kookli K, Nasirinezhad F (2020) The effect of chondroitinase ABC and photobiomodulation therapy on neuropathic pain after spinal cord injury in adult male rats. Physiol Behav 227:113141

    Article  CAS  PubMed  Google Scholar 

  12. da Silva EM, Mesquita-Ferrari RA, Rodrigues MFS, Magalhães EMR, Bussadori SK, De Brito A, de Moura MF, Souza NHC, Alves AN, Fernandes KPS (2020) The effects of photobiomodulation on inflammatory infiltrate during muscle repair in advanced-age rats. J Gerontol A Bio Sci Med Sci 75:437–441

    Google Scholar 

  13. Keshri GK, Yadav A, Verma S, Kumar B, Gupta A (2020) Effects of pulsed 810 nm Al-Ga-As diode laser on wound healing under immunosuppression: a molecular insight. Lasers Surg Med 52:424–436

    Article  PubMed  Google Scholar 

  14. Janzadeh A, Nasirinezhad F, Masoumipoor M, Jameie SB, Hayat P (2016) Photobiomodulation therapy reduces apoptotic factors and increases glutathione levels in a neuropathic pain model. Lasers Med Sci 31:1863–1869

    Article  PubMed  Google Scholar 

  15. Janzadeh A, Sarveazad A, Yousefifard M, Dameni S, Samani FS, Mokhtarian K, Nasirinezhad F (2017) Combine effect of Chondroitinase ABC and low level laser (660nm) on spinal cord injury model in adult male rats. Neuropeptides 65:90–99

    Article  CAS  PubMed  Google Scholar 

  16. Kang J, Cho SS, Kim HY, Lee BH, Cho HJ, Gwak YS (2020) Regional hyperexcitability and chronic neuropathic pain following spinal cord injury. Cell Mol Neurobiol 40:861–878

    Article  PubMed  Google Scholar 

  17. Werhagen L, Budh CN, Hultling C, Molander C (2004) Neuropathic pain after traumatic spinal cord injury-relations to gender, spinal level, completeness, and age at the time of injury. Spinal Cord 42:665–673

    Article  CAS  PubMed  Google Scholar 

  18. Sarveazad A, Janzadeh A, Taheripak G, Dameni S, Yousefifard M, Nasirinezhad F (2019) Co-administration of human adipose-derived stem cells and low-level laser to alleviate neuropathic pain after experimental spinal cord injury. Stem Cell Res Ther 10:183

    Article  PubMed  PubMed Central  Google Scholar 

  19. Kim D, Kim KR, Kwon Y, Kim M, Kim MJ, Sim Y, Ji H, Park J-J, Cho J-H, Choi H, Kim S (2020) AAV-mediated combination gene therapy for neuropathic pain: GAD65, GDNF, and IL-10. Mol Ther Methods Clin Dev 18:473–483

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Gou N, Wills-Karp M (2015) IL-4 and IL-13 signaling in allergic airway disease. Cytokine 75:68–78

    Article  Google Scholar 

  21. Fenn AM, Hall JCE, Gensel JC, Popovich PG, Godbout JP (2014) IL-4 signaling drives a unique arginase+/IL-1β+ microglia phenotype and recruits macrophages to the inflammatory CNS: consequences of age-related deficits in IL-4Rα after traumatic spinal cord injury. J Neurosci 34:8904–8917

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. David S, Kroner A (2011) Repertoire of microglial and macrophage responses after spinal cord injury. Nat Rev Neurosci 12:388–399

    Article  CAS  PubMed  Google Scholar 

  23. Tsuda M (2016) Microglia in the spinal cord and neuropathic pain. J Diabetes Investig 7:17–26

    Article  CAS  PubMed  Google Scholar 

  24. Kobashi S, Terashima T, Katagi M, Nakae Y, Okano J, Suzuki Y, Urushitani M, Kojima H (2020) Transplantation of M2-deviated microglia promotes recovery of motor function after spinal cord injury in mice. Mol Ther 28:254–265

    Article  CAS  PubMed  Google Scholar 

  25. Du X, Hao H, Yang Y, Huang S, Wang C, Gigout S, Ramli R, Li X, Jaworska E, Edwards I, Deuchars J, Yanagawa Y, Qi J, Guan B, Jaffe DB, Zhang H, Gamper N (2017) Local GABAergic signaling within sensory ganglia controls peripheral nociceptive transmission. J Clin Invest 127:1741–1756

    Article  PubMed  PubMed Central  Google Scholar 

  26. Smith DR, Dumont CM, Park J, Ciciriello AJ, Guo A, Tatineni R, Cummings BJ, Anderson AJ, Shea LD (2020) Polycistronic delivery of IL-10 and NT-3 promotes oligodendrocyte myelination and functional recovery in a mouse spinal cord injury model. Tissue Eng Part A 26:672–682

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Zhou Z, Peng X, Insolera R, Fink DJ, Mata M (2009) IL-10 promotes neuronal survival following spinal cord injury. Exp Neurol 220:183–190

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Hook MA, Washburn SN, Moreno G, Woller SA, Puga D, Lee KH, Grau JW (2011) An IL-1 receptor antagonist blocks a morphine-induced attenuation of locomotor recovery after spinal cord injury. Brain Behav Immun 25:349–359

    Article  CAS  PubMed  Google Scholar 

  29. Zong S, Zeng G, Wei B, Xiong C, Zhao Y (2012) Beneficial effect of interleukin-1 receptor antagonist protein on spinal cord injury recovery in the rat. Inflammation 35:520–526

    Article  CAS  PubMed  Google Scholar 

  30. Zhao W, Xie W, Xiao Q, Beers DR, Appel SH (2006) Protective effects of an anti-inflammatory cytokine, interleukin-4, on motoneuron toxicity induced by activated microglia. J Neurochem 99:1176–1187

    Article  CAS  PubMed  Google Scholar 

  31. Zhang X, Li G (2019) P2Y receptors in neuropathic pain. Pharmacol Biochem Behav 186:172788

    Article  CAS  PubMed  Google Scholar 

  32. Müller CE, Baqi Y, Namasivayam V (2020) Agonists and antagonists for purinergic receptors. In: Purinergic Signaling. Springer, New York, pp 45–64

    Chapter  Google Scholar 

  33. Malin SA, Molliver DC (2010) Gi- and Gq-coupled ADP (P2Y) receptors act in opposition to modulate nociceptive signaling and inflammatory pain behavior. Mol Pain 6:21

    Article  PubMed  PubMed Central  Google Scholar 

  34. Cantin LD, Bayrakdarian M, Buon C, Grazzini E, Hu Y-J, Labrecque J, Leung C, Luo X, Martino G, Paré M, Payza K, Popovic N, Projean D, Santhakumar V, Walpole C, Yu XH, Tomaszewski MJ (2012) Discovery of P2X3 selective antagonists for the treatment of chronic pain. Bioorg Med Chem Lett 22:2565–2571

    Article  CAS  PubMed  Google Scholar 

  35. Behroozi Z, Ramezani F, Janzadeh A, Rahimi B, Nasirinezhad F (2021) Platelet-rich plasma in umbilical cord blood reduces neuropathic pain in spinal cord injury by altering the expression of ATP receptors. Physiol Behav 228:113186

    Article  CAS  PubMed  Google Scholar 

  36. Gerevich Z, Illes P (2004) P2Y receptors and pain transmission. Purinergic Signal 1:3–10

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Patritti-Cram J, Coover RA, Jankowski MP, Ratner N (2021) Purinergic signaling in peripheral nervous system glial cells. Glia 69:1837–1851

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Hanani M, Huang TY, Cherkas PS, Ledda M, Pannese E (2002) Glial cell plasticity in sensory ganglia induced by nerve damage. Neuroscience 114:279–283

    Article  CAS  PubMed  Google Scholar 

  39. Chopra B, Gever J, Barrick SR, Hanna-Mitchell AT, Beckel JM, Ford APDW, Birder LA (2008) Expression and function of rat urothelial P2Y receptors. Am J Physiol Renal Physiol 294:F821–F829

    Article  CAS  PubMed  Google Scholar 

  40. Apostolidis A, Popat R, Yiangou Y, Cockayne D, Ford APDW, Davis JB, Dasgupta P, Fowler CJ, Anand P (2005) Decreased sensory receptors P2X3 and TRPV1 in suburothelial nerve fibers following intradetrusor injections of botulinum toxin for human detrusor overactivity. J Urol 174:977–982

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

The present study was financially supported by the research affairs of the Iran University of Medical Sciences (grant numbers 98-3-32-16267). The budget provided by the Iran University of Medical Sciences was used only to purchase materials and equipment.

Author information

Authors and Affiliations

Authors

Contributions

F.N designed and supervised the experiment and edited the final version of the manuscript. F.R carried out the western blotting. A.J carried out the surgeries on animals and wrote the manuscript under the supervision of F.N. M.H was consulted about the radiation therapy and English editing of the manuscript. N.M and S.Y carried out the behavioral test and radiation therapy.

Corresponding author

Correspondence to Farinaz Nasirinezhad.

Ethics declarations

Ethical approval

Experimental research protocol on animals was approved by the ethics committee of the Iran University of Medical Sciences. The ethical clearance number issued for the laboratory trial from IUMS was “IR.IUMS.REC.139.” All procedures were strictly conducted by the code of ethics.

Informed consent

N/A

Conflict of interest

The authors declare no competing interests.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Janzadeh, A., Ramezani, F., Yousefi, S. et al. Time-dependent photobiomodulation management of neuropathic pain induced by spinal cord injury in male rats. Lasers Med Sci 38, 120 (2023). https://doi.org/10.1007/s10103-023-03722-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s10103-023-03722-4

Keywords

Navigation