Table Info

Non-opioid medications	Other interventions	Non-pharmacologic strategies
Gabapentin, pregabalin, ketamine, nonsteroidal anti-inflammatory drug (NSAID), acetaminophen	Epidural, intravenous (IV) lidocaine, transcutaneous electrical nerve stimulation (TENS)	Physical therapy, cognitive behavioral therapy (CBT)

Declarations

Author contributions

AMC and SY equally contributed to: Conceptualization, Writing—original draft, Writing—review & editing. JT, SP, and BLW: Conceptualization, Writing—original draft, Writing—review & editing.

Conflicts of interest

The authors declare that they have no conflicts of interest.

Ethical approval

Not applicable.

Consent to participate

Not applicable.

Consent to publication

Not applicable.

Availability of data and materials

Not applicable.

Funding

Not applicable.

Copyright

References

Steadman J. Opiates and IV acetaminophen. Anesthesiology. 2019;130:513–4. [DOI] [PubMed]

Widerström-Noga E. Neuropathic pain and spinal cord injury: phenotypes and pharmacological management. Drugs. 2017;77:967–84. [DOI] [PubMed]

Gómara-Toldrà N, Sliwinski M, Dijkers MP. Physical therapy after spinal cord injury: a systematic review of treatments focused on participation. J Spinal Cord Med. 2014;37:371–9. [DOI] [PubMed] [PMC]

Mirea A, Leanca MC, Onose G, Sporea C, Padure L, Shelby ES, et al. Physical therapy and nusinersen impact on spinal muscular atrophy rehabilitative outcome. Front Biosci (Landmark Ed). 2022;27:179. [DOI] [PubMed]

Deer TR, Grider JS, Lamer TJ, Pope JE, Falowski S, Hunter CW, et al. A systematic literature review of spine neurostimulation therapies for the treatment of pain. Pain Med. 2020;21:1421–32. [DOI] [PubMed]

Deer TR, Skaribas IM, Haider N, Salmon J, Kim C, Nelson C, et al. Effectiveness of cervical spinal cord stimulation for the management of chronic pain. Neuromodulation. 2014;17:265–71. [DOI] [PubMed]

Schmidt GL. The use of spinal cord stimulation/neuromodulation in the management of chronic pain. J Am Acad Orthop Surg. 2019;27:e401–7. [DOI] [PubMed]

Hofmann SG, Asnaani A, Vonk IJJ, Sawyer AT, Fang A. The efficacy of cognitive behavioral therapy: a review of meta-analyses. Cogn Ther Res. 2012;36:427–40. [DOI] [PubMed] [PMC]

Parrish JM, Jenkins NW, Parrish MS, Cha EDK, Lynch CP, Massel DH, et al. The influence of cognitive behavioral therapy on lumbar spine surgery outcomes: a systematic review and meta-analysis. Eur Spine J. 2021;30:1365–79. [DOI] [PubMed]

10.

Scarone P, Smeets AYJM, van Kuijk SMJ, van Santbrink H, Peters M, Koetsier E. A randomized controlled TRIal of cognitive BEhavioral therapy for high Catastrophizing in patients undergoing lumbar fusion surgery: the TRIBECA study. BMC Musculoskelet Disord. 2020;21:810. [DOI] [PubMed] [PMC]

11.

Kerai S, Saxena KN, Taneja B, Sehrawat L. Role of transcutaneous electrical nerve stimulation in post-operative analgesia. Indian J Anaesth. 2014;58:388–93. [DOI] [PubMed] [PMC]

12.

Santos CM, Francischi JN, Lima-Paiva P, Sluka KA, Resende MA. Effect of transcutaneous electrical stimulation on nociception and edema induced by peripheral serotonin. Int J Neurosci. 2013;123:507–15. [DOI] [PubMed]

13.

Gibson W, Wand BM, Meads C, Catley MJ, O’Connell NE. Transcutaneous electrical nerve stimulation (TENS) for chronic pain ‐ an overview of Cochrane Reviews. Cochrane Database Syst Rev. 2019;2019:CD011890. [DOI] [PubMed] [PMC]

14.

Schuster GD, Infante MC. Pain relief after low back surgery: the efficacy of transcutaneous electrical nerve stimulation. Pain. 1980;8:299–302. [DOI] [PubMed]

15.

Agarwal D, Chahar P, Chmiela M, Sagir A, Kim A, Malik F, et al. Multimodal analgesia for perioperative management of patients presenting for spinal surgery. Curr Pharm Des. 2019;25:2123–32. [DOI] [PubMed]

16.

Vadivelu N, Kai AM, Tran D, Kodumudi G, Legler A, Ayrian E. Options for perioperative pain management in neurosurgery. J Pain Res. 2016;9:37–47. [DOI] [PubMed] [PMC]

17.

Wewalka M. Interventional pain management for spinal disorders: a review of injection techniques. Wien Med Wochenschr. 2016;166:48–53. [DOI] [PubMed]

18.

Guilfoyle MR, Mannion RJ, Mitchell P, Thomson S. Epidural fentanyl for postoperative analgesia after lumbar canal decompression: a randomized controlled trial. Spine J. 2012;12:646–51. [DOI] [PubMed]

19.

Gkegkes ID, Minis EE, Iavazzo C. Oxycodone/naloxone in postoperative pain management of surgical patients. J Opioid Manag. 2018;14:52–60. [DOI] [PubMed]

20.

Mielau J, Vogel M, Gutwinski S, Mick I. New approaches in drug dependence: opioids. Curr Addict Rep. 2021;8:298–305. [DOI] [PubMed] [PMC]

21.

Kupfer M, Formal CS. Non-opioid pharmacologic treatment of chronic spinal cord injury-related pain. J Spinal Cord Med. 2022;45:163–72. [DOI] [PubMed] [PMC]

22.

Strang J, Volkow ND, Degenhardt L, Hickman M, Johnson K, Koob GF, et al. Opioid use disorder. Nat Rev Dis Primers. 2020;6:3. [DOI] [PubMed]

23.

Bajwa SJ, Haldar R. Pain management following spinal surgeries: an appraisal of the available options. J Craniovertebr Junction Spine. 2015;6:105–10. [DOI] [PubMed] [PMC]

24.

Bianconi M, Ferraro L, Ricci R, Zanoli G, Antonelli T, Giulia B, et al. The pharmacokinetics and efficacy of ropivacaine continuous wound instillation after spine fusion surgery. Anesth Analg. 2004;98:166–72. [DOI] [PubMed]

25.

Murphy TM. Chronic opioids for chronic low back pain—solution or problem? J Am Board Fam Pract. 1996;9:225–8. [PubMed]

26.

Reed LA, Patel M, Luque K, Theiss SM. Opioid sparing analgesics in spine surgery. Adv Orthop. 2022;2022:1026547. [DOI] [PubMed] [PMC]

27.

Chen EY, Betancourt L, Li L, Trucks E, Marcantonio A, Tornetta P 3rd. Standardized, patient-specific, postoperative opioid prescribing after inpatient orthopaedic surgery. J Am Acad Orthop Surg. 2020;28:e304–18. [DOI] [PubMed]

28.

Brown RL, Fleming MF, Patterson JJ. Chronic opioid analgesic therapy for chronic low back pain. J Am Board Fam Pract. 1996;9:191–204. [PubMed]

29.

Deyo RA, Hallvik SE, Hildebran C, Marino M, O’Kane N, Carson J, et al. Use of prescription opioids before and after an operation for chronic pain (lumbar fusion surgery). Pain. 2018;159:1147–54. [DOI] [PubMed] [PMC]

30.

Brummett CM, Waljee JF, Goesling J, Moser S, Lin P, Englesbe MJ, et al. New persistent opioid use after minor and major surgical procedures in US adults. JAMA Surg. 2017;152:e170504. [DOI] [PubMed] [PMC]

31.

Orosz LD, Yamout T. The opioid crisis as it pertains to spine surgery. J Spine Surg. 2023;9:9–12. [DOI] [PubMed] [PMC]

32.

Prabhakar NK, Chadwick AL, Nwaneshiudu C, Aggarwal A, Salmasi V, Lii TR, et al. Management of postoperative pain in patients following spine surgery: a narrative review. Int J Gen Med. 2022;15:4535–49. [DOI] [PubMed] [PMC]

33.

Dey S, Vrooman BM. Alternatives to opioids for managing pain [Internet]. StatPearls Publishing LLC; 2024 [cited 2024 Jan 5]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK574543/

34.

Benyamin R, Trescot AM, Datta S, Buenaventura R, Adlaka R, Sehgal N, et al. Opioid complications and side effects. Pain Physician. 2008;11:S105–20. [PubMed]

35.

Licina A, Silvers A. Perioperative multimodal analgesia for adults undergoing surgery of the spine—a systematic review and meta-analysis of three or more modalities. World Neurosurg. 2022;163:11–23. [DOI] [PubMed]

36.

Chou R, Gordon DB, de Leon-Casasola OA, Rosenberg JM, Bickler S, Brennan T, et al. Management of postoperative pain: a clinical practice guideline from the American Pain Society, the American Society of Regional Anesthesia and Pain Medicine, and the American Society of Anesthesiologists’ Committee on Regional Anesthesia, Executive Committee, and Administrative Council. J Pain. 2016;17:131–57. [DOI] [PubMed]

37.

Vane JR, Botting RM. Anti-inflammatory drugs and their mechanism of action. Inflamm Res. 1998;47:78–87. [DOI] [PubMed]

38.

Zhang Z, Xu H, Zhang Y, Li W, Yang Y, Han T, et al. Nonsteroidal anti-inflammatory drugs for postoperative pain control after lumbar spine surgery: a meta-analysis of randomized controlled trials. J Clin Anesth. 2017;43:84–9. [DOI]

39.

Sivaganesan A, Chotai S, White-Dzuro G, McGirt MJ, Devin CJ. The effect of NSAIDs on spinal fusion: a cross-disciplinary review of biochemical, animal, and human studies. Eur Spine J. 2017;26:2719–28. [DOI] [PubMed]

40.

Ohashi N, Kohno T. Analgesic effect of acetaminophen: a review of known and novel mechanisms of action. Front Pharmacol. 2020;11:580289. [DOI] [PubMed] [PMC]

41.

Freo U. Paracetamol for multimodal analgesia. Pain Manag. 2022;12:737–50. [DOI] [PubMed]

42.

Rivkin A, Rivkin MA. Perioperative nonopioid agents for pain control in spinal surgery. Am J Health Syst Pharm. 2014;71:1845–57. [DOI] [PubMed]

43.

Sills GJ. The mechanisms of action of gabapentin and pregabalin. Curr Opin Pharmacol. 2006;6:108–13. [DOI] [PubMed]

44.

Risher WC, Eroglu C. Emerging roles for α2δ subunits in calcium channel function and synaptic connectivity. Curr Opin Neurobiol. 2020;63:162–9. [DOI] [PMC]

45.

Hurley RW, Cohen SP, Williams KA, Rowlingson AJ, Wu CL. The analgesic effects of perioperative gabapentin on postoperative pain: a meta-analysis. Reg Anesth Pain Med. 2006;31:237–47. [DOI] [PubMed]

46.

Barrett W, Buxhoeveden M, Dhillon S. Ketamine: a versatile tool for anesthesia and analgesia. Curr Opin Anaesthesiol. 2020;33:633–8. [DOI] [PubMed]

47.

Barreveld AM, Correll DJ, Liu X, Max B, McGowan JA, Shovel L, et al. Ketamine decreases postoperative pain scores in patients taking opioids for chronic pain: results of a prospective, randomized, double-blind study. Pain Med. 2013;14:925–34. [DOI] [PubMed]

48.

Murphy GS, Avram MJ, Greenberg SB, Benson J, Bilimoria S, Maher CE, et al. Perioperative methadone and ketamine for postoperative pain control in spinal surgical patients: a randomized, double-blind, placebo-controlled trial. Anesthesiology. 2021;134:697–708. [DOI] [PubMed]

49.

Butterworth JF, Strichartz GR. Molecular mechanisms of local anesthesia: a review. Anesthesiology. 1990;72:711–34. [DOI] [PubMed]

50.

Abelson KS, Höglund AU. Intravenously administered lidocaine in therapeutic doses increases the intraspinal release of acetylcholine in rats. Neurosci Lett. 2002;317:93–6. [DOI] [PubMed]

51.

Kurabe M, Furue H, Kohno T. Intravenous administration of lidocaine directly acts on spinal dorsal horn and produces analgesic effect: an in vivo patch-clamp analysis. Sci Rep. 2016;6:26253. [DOI] [PubMed] [PMC]

52.

Woolf CJ, Wiesenfeld-Hallin Z. The systemic administration of local anaesthetics produces a selective depression of C-afferent fibre evoked activity in the spinal cord. Pain. 1985;23:361–74. [DOI] [PubMed]

53.

Ibrahim A, Aly M, Farrag W. Effect of intravenous lidocaine infusion on long-term postoperative pain after spinal fusion surgery. Medicine (Baltimore). 2018;97:e0229. [DOI] [PubMed] [PMC]

54.

Ziemichod W, Kotlinska J, Gibula-Tarlowska E, Karkoszka N, Kedzierska E. Cebranopadol as a novel promising agent for the treatment of pain. Molecules. 2022;27:3987. [DOI] [PubMed] [PMC]

55.

Webb MP, Helander EM, Menard BL, Urman RD, Kaye AD. Tanezumab: a selective humanized mAb for chronic lower back pain. Ther Clin Risk Manag. 2018;14:361–7. [DOI] [PubMed] [PMC]

56.

Kehlet H. Surgical stress: the role of pain and analgesia. Br J Anaesth. 1989;63:189–95. [DOI] [PubMed]

57.

Bruehl S, Apkarian AV, Ballantyne JC, Berger A, Borsook D, Chen WG, et al. Personalized medicine and opioid analgesic prescribing for chronic pain: opportunities and challenges. J Pain. 2013;14:103–13. [DOI] [PubMed] [PMC]

58.

Baratta JL, Schwenk ES, Viscusi ER. Clinical consequences of inadequate pain relief: barriers to optimal pain management. Plast Reconstr Surg. 2014;134:15S–21S. [DOI] [PubMed]