Background & Aims
Opioids are commonly used for recreational purpose globally. Heroin is most commonly abused opioid in India [1]. Opioids affect innate immunity through toll-like receptor (TLR) and acquired immunity through its effects on T lymphocyte subsets (CD3, CD4 and CD8 cells) [2]. Lipopolysaccharide induced TLR-4 signaling might be associated with opioid induced hyperalgesia peripherally. The interaction of opioids with glial TLR-4 may affect opioid craving and recreational use [3]. Opioid agonist treatment (OAT) is an evidence-based treatment for opioid use disorder (OUD). It improves opioid withdrawal, craving and blocks the reinforcing effect of illicit opioid in patients [4].
There is a dearth of published human studies on the immunological correlates of opioid withdrawal related pain. So, we designed a longitudinal study to tease out relationship of immunological markers and pain in patients with OUD on OAT.
Methods
We included 34 consenting adults with opioid dependence, with or without tobacco dependence, having no other inflammatory conditions. We assessed the opioid dependence severity [5], craving for opioid [6], using specific instruments. Pain was assessed using Brief pain inventory Short Form (BPI-SF) [7].
Plasma TLR-4 was assessed using Enzyme Linked Immunosorbent Assay (ELISA), with the help of ELISA-kit Bioassay Tech Lab (Cat no.: E0346Hu). We measured neutrophil count, CD3, CD4 and CD8 T cell count using flow cytometry of EDTA blood samples [8,9].
After one month of sublingual buprenorphine-naloxone combination treatment, pain, craving, immune markers and dependence severity were again assessed in this group. We analyzed the data using statistical package for social sciences software version 21 (ref). Appropriate descriptive and inferential statistics were used. Pearson’s correlation was used to assess correlation between the pain symptoms and immune markers.
Results
There was significant improvement in pain severity [baseline: 5.6±1.7; follow up: 0.7±0.4 t(df): 17.7(33); p<.001] and interference due to pain [baseline: 7.1±1.6; follow up: 0.2±0.3; t(df): 25.8(33); p<.001] after one month of buprenorphine maintenance (mean dose: 4.7±2.1 mg) treatment. The mean TLR-4 level significantly increased [baseline: 2.9±0.8ng/ml; follow up: 3.5±1.2ng/ml t(df): -.5(33); p=.001] on follow up. Mean CD3, CD4 and CD8 T cell counts increased whereas absolute neutrophil count decreased on follow up. The changes were not statistically significant. There was no correlation between the BPI-SF severity and interference score with TLR-4 level, neutrophil count and T cell subset counts (CD3, CD4 and CD8 T cells) at baseline or during follow up assessment. On multivariate analysis, baseline immune markers did not predict either the final pain severity, or the interference due to pain in both the injecting drug user (IDU) and non-IDU group.
Conclusions
The significant improvement in pain severity and interference due to pain, severity of opioid dependence and craving scores after one month demonstrate the beneficial effect of OAT on opioid craving and withdrawal. Along with this clinical improvement, innate immunity marker TLR-4 showed significant improvement along with a non-significant trend of improvement in acquired immunity. These suggest immunological recovery in our study participants. Our study did not find significant prediction of withdrawal related pain by baseline immune markers but it requires a larger and longer study to confirm these findings.
References
1.UNODC. World Drug Report 2023. Vienna, Austria: UNODC; 2023. (Sales No. E.23.XI.7; vol. 2).
2.Ninkovi? J, Roy S. Role of the mu-opioid receptor in opioid modulation of immune function. Amino Acids. 2013;45(1):9-24.
3.Hutchinson MR, Northcutt AL, Hiranita T, Wang X, Lewis SS, Thomas J, et al. Opioid activation of toll-like receptor 4 contributes to drug reinforcement. J Neurosci. 2012;32:11187-11200.
4.Shulman M, Wai JM, Nunes EV. Buprenorphine Treatment for Opioid Use Disorder: An Overview. CNS Drugs. 2019 Jun;33(6):567-580.
5.Sutherland G, Edwards G, Taylor C, Phillips G, Gossop M, Brady R. The measurement of opiate dependence. Br J Addict. 1986;81:485-494
6.Franken IH, Hendriks VM, van den Brink W. Initial validation of two opiate craving questionnaires: the Obsessive Compulsive Drug Use Scale and the Desires for Drug Questionnaire. Addict Behav. 2002;27:675-685.
7.Cleeland CS, Ryan KM. Pain assessment: global use of the Brief Pain Inventory. Ann. Acad. Med. Singap. 1994;23:129-138.
8.Bioassay Tech Lab. Human Toll-like Receptor 4, TLR4 ELISA Kit – BT LAB [Internet]. Bioassay Tech Lab; [cited 2024 Jan 29]. Available from: https://www.bt-laboratory.com/index.php/Shop/Index/productShijiheDetail/p_id/328.html
9.Bdbiosciences. bd_lsrfortessa_ brochure [Internet]. Bdbiosciences; [cited 2022 Feb 3]. Available from: https://www.bdbiosciences.com/content/dam/bdb/marketing-documents /bd_lsrfortessa_ brochure.pdf
10.SPSS Inc. Released 2012. SPSS for Windows, Version 21.0. Chicago, SPSS Inc.
Presenting Author
Debasish Basu
Poster Authors
Topics
- Other