A Review of Studies on the Use of New Non-Gabapentinoid Anticonvulsants and Muscle Relaxants in the Control of Acute Postoperative Pain
Abstract
Postoperative pain management in any type of surgery is an important issue for patients. The pain relief contributes to decreased hospital costs, shorter hospital stay, and elevated patient consent. Correspondingly, in this review article we assessed the postoperative pain management efficacy of new non-gabapentinoid anticonvulsants and muscle relaxant drugs in pre-clinical and clinical studies. The scientific databases, including PubMed, Embase, Scopus, and Google Scholar, were searched using relevant keywords: surgery, postoperative pain, analgesia, non-gabapentinoid anticonvulsants, and muscle relaxants. New anticonvulsants reduce postoperative pain, length of stay at postoperative anesthesia care unit, and analgesic requirement after surgeries. Their mechanisms include the inhibition of glutamate release, blocking the N-type calcium channels of afferent neurons, inhibition of supraspinal 5-hydroxytryptamine-3 receptor, and prevention of cyclin-dependent kinase 5-mediated collapsin response mediator protein 2 phosphorylation. Also, muscle relaxants show the same effects by downregulation the Cacna1a, Cacna1b, and Runt-related transcription factor 1 genes of dorsal root ganglia, inhibition the release of glutamate, aspartate or substance P from the terminals of primary afferent C and Aδ fibers, expression of Neurokinin 1 receptor in the spinal dorsal horn, agonistic effect on α2-adrenoceptor, and stimulation of acetylcholine release in the spinal cord. With respect to the concerns regarding opioid abuse, muscle relaxants and non-gabapentinoid anticonvulsant drugs can be regarded as a safe option for postoperative pain control.
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2. Finnerup NB. Nonnarcotic Methods of Pain Management. New Engl J Med 2019;380(25):2440-8.
3. Kent ML, Tighe PJ, Belfer I, et al. The ACTTION–APS–AAPM Pain Taxonomy (AAAPT) multidimensional approach to classifying acute pain conditions. Pain Med 2017;18(5):947-58.
4. Abdolrazaghnejad A, Banaie M, Tavakoli N, Safdari M, Rajabpour-Sanati A. Pain Management in the Emergency Department: a Review Article on Options and Methods. Adv J Emerg Med 2018;2(4):e45.
5. O'Connor TM, O'Connell J, O'Brien DI, Goode T, Bredin CP, Shanahan F. The role of substance P in inflammatory disease. J Cell Physiol 2004;201(2):167-80.
6. Carozzi VA, Canta A, Oggioni N, et al. Expression and distribution of 'high affinity' glutamate transporters GLT1, GLAST, EAAC1 and of GCPII in the rat peripheral nervous system. J Anat 2008;213(5):539-46.
7. Wells N, Pasero C, McCaffery M. Improving the Quality of Care Through Pain Assessment and Management. In: Hughes RG, editor. Patient Safety and Quality: An Evidence-Based Handbook for Nurses. Rockville (MD): Agency for Healthcare Research and Quality (US); 2008 Apr. Chapter 17. Available from: https://www.ncbi.nlm.nih.gov/books/NBK2658/
8. Garimella V, Cellini C. Postoperative pain control. Clin Colon Rectal Surg 2013;26(3):191-6.
9. Bonicalzi V, Canavero S, Cerutti F, Piazza M, Clemente M, Chió A. Lamotrigine reduces total postoperative analgesic requirement: A randomized double-blind, placebo-controlled pilot study. Surgery 1997;122(3):567-70.
10. Bhosale UA, Yegnanarayan R, Gupta A, Shah P, Sardesai S. Comparative pre-emptive analgesic efficacy study of novel antiepileptic agents gabapentin, lamotrigine and topiramate in patients undergoing major surgeries at a tertiary care hospital: a randomized double blind clinical trial. J Basic Clin Physiol Pharmacol 2017;28(1):59-66.
11. Gupta A, Bhosale UA, Shah P, Yegnanarayan R, Sardesai S. Comparative pre-emptive analgesic efficacy study of novel antiepileptic agents lamotrigine and topiramate in patients undergoing major surgeries at a tertiary care hospital: a randomized double blind clinical trial. Ann Neurosci 2016;23(3):162-70.
12. Shah P, Bhosale UA, Gupta A, Yegnanarayan R, Sardesai S. A randomized double-blind placebo-controlled study to compare preemptive analgesic efficacy of novel antiepileptic agent lamotrigine in patients undergoing major surgeries. N Am J Med Sci 2016;8(2):93-9.
13. Modanloo H, Eftekharian H, Arabiun H. Postoperative pain management after impacted third molar surgery with preoperative oral lamotrigine, a randomized, double-blind, placebo-controlled trial. J Dent 2018;19(3):189-96.
14. Moutal A, Chew LA, Yang X, et al. (S)-lacosamide inhibition of CRMP2 phosphorylation reduces postoperative and neuropathic pain behaviors through distinct classes of sensory neurons identified by constellation pharmacology. Pain 2016;157(7):1448.
15. Monge-Márquez ME, Márquez-Rivas J, Mayorga-Buiza MJ, Rivero-Garvía M. Lacosamide as an alternative in the treatment of post-surgery neuropathic pain in an allergic patient. Rev Neurol 2013;57(7):313-6.
16. Das SK, Choupoo NS, Momin K, Das N, Das H, Sohkhia WER. A single preoperative dose of levetiracetam has no effect on pain or analgesic requirements after laparoscopic cholecystectomy. Eur J Anaesthesiol 2015;32(4):278-80.
17. Sliva J, Dolezal T, Prochazkova M, Votava M, Krsiak M. Preemptive levetiracetam decreases postoperative pain in rats. Neuro Endocrinol Lett 2008;29(6):953-7.
18. Burchiel KJ, Hsu FP. Pain and spasticity after spinal cord injury: mechanisms and treatment. Spine 2001;26(24S):S146-S60.
19. Mueller A, Starobova H, Morgan M, et al. Antiallodynic effects of the selective NaV1.7 inhibitor Pn3a in a mouse model of acute postsurgical pain: evidence for analgesic synergy with opioids and baclofen. Pain 2019;160(8).
20. Corli O, Roma G, Bacchini M, et al. Double-blind placebo-controlled trial of baclofen, alone and in combination, in patients undergoing voluntary abortion. Clin Ther 1984;6(6):800-7.
21. Bojaxhi E, Salek DR, Sherman CE, Greengrass RA. Regional anesthesia for a total knee arthroplasty on an adult patient with spastic diplegia and an intrathecal baclofen pump. Rom J Anaesth Intensive Care 2017;24(1):69.
22. Blumenkopf B. Combination Analgesic-Antispasmodic Therapy in Postoperative Pain. Spine 1987;12(4):384-7.
23. Sanders JC, Gerstein N, Torgeson E, Abram S. Intrathecal baclofen for postoperative analgesia after total knee arthroplasty. J Clin Anesth 2009;21(7):486-92.
24. Ala S, Alvandipour M, Saeedi M, Mansourifar M, Monajati M, Shiva A. Effect of topical baclofen 5% on post-hemorrhoidectomy pain: randomized double blind placebo-controlled clinical trial. J Gastrointest Surg 2020;24(2):405-10.
25. Nemeth BA, Montero RJ, Halanski MA, Noonan KJ. Epidural baclofen for the management of postoperative pain in children with cerebral palsy. J Pediatr Orthop 2015;35(6):571-5.
26. Schneider MS. Pain reduction in breast augmentation using methocarbamol. aesthetic plast. Surg 1997;21(1):23-4.
27. Hidalgo DA, Pusic AL. The role of methocarbamol and intercostal nerve blocks for pain management in breast augmentation. Aesthet Surg J 2005;25(6):571-5.
28. Schneider MS. Methocarbamol: Adjunct therapy for pain management in breast augmentation. Aesthet Surg J.2002;22(4):380-1.
29. Looke TD, Kluth CT. Effect of preoperative intravenous methocarbamol and intravenous acetaminophen on opioid use after primary total hip and knee replacement. Orthopedics 2013;36(2):25-32.
30. Shakeri H, Mianroodi A, Haghbin M, Khanjani N. The efficacy of oral tizanidine in reducing pain after septoplasty. Tehran Univ Med J 2020;78(3):144-9.
31. Imanaga K, Wajima Zi, Inoue T, Ogawa R. Effect of oral tizanidine on local-anesthetic infiltration pain during epidural catheterization. J Nippon Med Sch 2004;71(2):105-10.
32. Talakoub R, Abbasi S, Maghami E, Zavareh SM. The effect of oral tizanidine on postoperative pain relief after elective laparoscopic cholecystectomy. Adv Biomed Res 2016;5:19.
33. Ahiskalioglu A, Yayik AM, Oral Ahiskalioglu E, et al. Ultrasound-guided bilateral superficial cervical block and preemptive single-dose oral tizanidine for post-thyroidectomy pain: a randomized-controlled double-blind study. J Anesth 2018;32(2):219-26.
34. Omote K, Satoh O, Sonoda H, Kumeta Y, Yamaya K, Namiki A. Effects of oral alpha 2 adrenergic agonists, clonidine and tizanidine, on tetracaine spinal anesthesia. Masui 1995;44(6):816-23.
35. Yazicioğlu D, Caparlar C, Akkaya T, Mercan U, Kulaçoğlu H. Tizanidine for the management of acute postoperative pain after inguinal hernia repair: A placebo-controlled double-blind trial. Eur J Anaesthesiol 2016;33(3):215-22.
36. Kirmeier R, Truschnegg A, Payer M, Acham S, Schulz K, Jakse N. Evaluation of a muscle relaxant on sequelae of third molar surgery: a pilot study. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2007;104(3):e8-14.
37. Rupani M, Alijanpour E, Banihashem N, et al. Effect of Oral Tizanidine on Postoperative Pain after Perianal Surgery. J Babol Univ Med Sci 2013;15(4):7-11.
38. Vatankhah M, Jarineshin H, Malakshoar M. Effect of oral Tizanidine on postoperative pain herniorrhaphy. Journal of Medical Council of Iran 2017;35(2):167-74.
39. Taheri A, Hashemian M, Noroozi M, Bakhtiari M, Doroodian MR, Salajegheh S. Effect of oral tizanidine on prolongation of intrathecal lidocaine. J Emerg Prac Trauma 2018;4(2):62-6.
40. Hord A, Chalfoun AG, Denson D, Azevedo MI. Systemic tizanidine hydrochloride (zanafle™") relieves thermal hyperalgesia in rats with an experimental mononeuropathy. Anesth Analg 2001;93(5):1307-9.
41. de Santana Santos T, Calazans AC, Martins-Filho PR, Silva LC, de Oliveira ESED, Gomes AC. Evaluation of the muscle relaxant cyclobenzaprine after third-molar extraction. J Am Dent Assoc (1939) 2011;142(10):1154-62.
42. Gilron I. Review article: the role of anticonvulsant drugs in postoperative pain management: a bench-to-bedside perspective. Can J Anaesth 2006;53(6):562-71.
43. Beebe FA, Barkin RL, Barkin S. A clinical and pharmacologic review of skeletal muscle relaxants for musculoskeletal conditions. Am J Ther 2005;12(2):151-71.
44. Sibrack J, Hammer R. Methocarbamol. StatPearls. Treasure Island FL: © 2021, StatPearls Publishing LLC.; 2021.
45. Honda M, Sekiguchi Y, Sato N, Ono H. Involvement of imidazoline receptors in the centrally acting muscle-relaxant effects of tizanidine. Eur J Pharmacol 2002;445(3):187-93.
2. Finnerup NB. Nonnarcotic Methods of Pain Management. New Engl J Med 2019;380(25):2440-8.
3. Kent ML, Tighe PJ, Belfer I, et al. The ACTTION–APS–AAPM Pain Taxonomy (AAAPT) multidimensional approach to classifying acute pain conditions. Pain Med 2017;18(5):947-58.
4. Abdolrazaghnejad A, Banaie M, Tavakoli N, Safdari M, Rajabpour-Sanati A. Pain Management in the Emergency Department: a Review Article on Options and Methods. Adv J Emerg Med 2018;2(4):e45.
5. O'Connor TM, O'Connell J, O'Brien DI, Goode T, Bredin CP, Shanahan F. The role of substance P in inflammatory disease. J Cell Physiol 2004;201(2):167-80.
6. Carozzi VA, Canta A, Oggioni N, et al. Expression and distribution of 'high affinity' glutamate transporters GLT1, GLAST, EAAC1 and of GCPII in the rat peripheral nervous system. J Anat 2008;213(5):539-46.
7. Wells N, Pasero C, McCaffery M. Improving the Quality of Care Through Pain Assessment and Management. In: Hughes RG, editor. Patient Safety and Quality: An Evidence-Based Handbook for Nurses. Rockville (MD): Agency for Healthcare Research and Quality (US); 2008 Apr. Chapter 17. Available from: https://www.ncbi.nlm.nih.gov/books/NBK2658/
8. Garimella V, Cellini C. Postoperative pain control. Clin Colon Rectal Surg 2013;26(3):191-6.
9. Bonicalzi V, Canavero S, Cerutti F, Piazza M, Clemente M, Chió A. Lamotrigine reduces total postoperative analgesic requirement: A randomized double-blind, placebo-controlled pilot study. Surgery 1997;122(3):567-70.
10. Bhosale UA, Yegnanarayan R, Gupta A, Shah P, Sardesai S. Comparative pre-emptive analgesic efficacy study of novel antiepileptic agents gabapentin, lamotrigine and topiramate in patients undergoing major surgeries at a tertiary care hospital: a randomized double blind clinical trial. J Basic Clin Physiol Pharmacol 2017;28(1):59-66.
11. Gupta A, Bhosale UA, Shah P, Yegnanarayan R, Sardesai S. Comparative pre-emptive analgesic efficacy study of novel antiepileptic agents lamotrigine and topiramate in patients undergoing major surgeries at a tertiary care hospital: a randomized double blind clinical trial. Ann Neurosci 2016;23(3):162-70.
12. Shah P, Bhosale UA, Gupta A, Yegnanarayan R, Sardesai S. A randomized double-blind placebo-controlled study to compare preemptive analgesic efficacy of novel antiepileptic agent lamotrigine in patients undergoing major surgeries. N Am J Med Sci 2016;8(2):93-9.
13. Modanloo H, Eftekharian H, Arabiun H. Postoperative pain management after impacted third molar surgery with preoperative oral lamotrigine, a randomized, double-blind, placebo-controlled trial. J Dent 2018;19(3):189-96.
14. Moutal A, Chew LA, Yang X, et al. (S)-lacosamide inhibition of CRMP2 phosphorylation reduces postoperative and neuropathic pain behaviors through distinct classes of sensory neurons identified by constellation pharmacology. Pain 2016;157(7):1448.
15. Monge-Márquez ME, Márquez-Rivas J, Mayorga-Buiza MJ, Rivero-Garvía M. Lacosamide as an alternative in the treatment of post-surgery neuropathic pain in an allergic patient. Rev Neurol 2013;57(7):313-6.
16. Das SK, Choupoo NS, Momin K, Das N, Das H, Sohkhia WER. A single preoperative dose of levetiracetam has no effect on pain or analgesic requirements after laparoscopic cholecystectomy. Eur J Anaesthesiol 2015;32(4):278-80.
17. Sliva J, Dolezal T, Prochazkova M, Votava M, Krsiak M. Preemptive levetiracetam decreases postoperative pain in rats. Neuro Endocrinol Lett 2008;29(6):953-7.
18. Burchiel KJ, Hsu FP. Pain and spasticity after spinal cord injury: mechanisms and treatment. Spine 2001;26(24S):S146-S60.
19. Mueller A, Starobova H, Morgan M, et al. Antiallodynic effects of the selective NaV1.7 inhibitor Pn3a in a mouse model of acute postsurgical pain: evidence for analgesic synergy with opioids and baclofen. Pain 2019;160(8).
20. Corli O, Roma G, Bacchini M, et al. Double-blind placebo-controlled trial of baclofen, alone and in combination, in patients undergoing voluntary abortion. Clin Ther 1984;6(6):800-7.
21. Bojaxhi E, Salek DR, Sherman CE, Greengrass RA. Regional anesthesia for a total knee arthroplasty on an adult patient with spastic diplegia and an intrathecal baclofen pump. Rom J Anaesth Intensive Care 2017;24(1):69.
22. Blumenkopf B. Combination Analgesic-Antispasmodic Therapy in Postoperative Pain. Spine 1987;12(4):384-7.
23. Sanders JC, Gerstein N, Torgeson E, Abram S. Intrathecal baclofen for postoperative analgesia after total knee arthroplasty. J Clin Anesth 2009;21(7):486-92.
24. Ala S, Alvandipour M, Saeedi M, Mansourifar M, Monajati M, Shiva A. Effect of topical baclofen 5% on post-hemorrhoidectomy pain: randomized double blind placebo-controlled clinical trial. J Gastrointest Surg 2020;24(2):405-10.
25. Nemeth BA, Montero RJ, Halanski MA, Noonan KJ. Epidural baclofen for the management of postoperative pain in children with cerebral palsy. J Pediatr Orthop 2015;35(6):571-5.
26. Schneider MS. Pain reduction in breast augmentation using methocarbamol. aesthetic plast. Surg 1997;21(1):23-4.
27. Hidalgo DA, Pusic AL. The role of methocarbamol and intercostal nerve blocks for pain management in breast augmentation. Aesthet Surg J 2005;25(6):571-5.
28. Schneider MS. Methocarbamol: Adjunct therapy for pain management in breast augmentation. Aesthet Surg J.2002;22(4):380-1.
29. Looke TD, Kluth CT. Effect of preoperative intravenous methocarbamol and intravenous acetaminophen on opioid use after primary total hip and knee replacement. Orthopedics 2013;36(2):25-32.
30. Shakeri H, Mianroodi A, Haghbin M, Khanjani N. The efficacy of oral tizanidine in reducing pain after septoplasty. Tehran Univ Med J 2020;78(3):144-9.
31. Imanaga K, Wajima Zi, Inoue T, Ogawa R. Effect of oral tizanidine on local-anesthetic infiltration pain during epidural catheterization. J Nippon Med Sch 2004;71(2):105-10.
32. Talakoub R, Abbasi S, Maghami E, Zavareh SM. The effect of oral tizanidine on postoperative pain relief after elective laparoscopic cholecystectomy. Adv Biomed Res 2016;5:19.
33. Ahiskalioglu A, Yayik AM, Oral Ahiskalioglu E, et al. Ultrasound-guided bilateral superficial cervical block and preemptive single-dose oral tizanidine for post-thyroidectomy pain: a randomized-controlled double-blind study. J Anesth 2018;32(2):219-26.
34. Omote K, Satoh O, Sonoda H, Kumeta Y, Yamaya K, Namiki A. Effects of oral alpha 2 adrenergic agonists, clonidine and tizanidine, on tetracaine spinal anesthesia. Masui 1995;44(6):816-23.
35. Yazicioğlu D, Caparlar C, Akkaya T, Mercan U, Kulaçoğlu H. Tizanidine for the management of acute postoperative pain after inguinal hernia repair: A placebo-controlled double-blind trial. Eur J Anaesthesiol 2016;33(3):215-22.
36. Kirmeier R, Truschnegg A, Payer M, Acham S, Schulz K, Jakse N. Evaluation of a muscle relaxant on sequelae of third molar surgery: a pilot study. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2007;104(3):e8-14.
37. Rupani M, Alijanpour E, Banihashem N, et al. Effect of Oral Tizanidine on Postoperative Pain after Perianal Surgery. J Babol Univ Med Sci 2013;15(4):7-11.
38. Vatankhah M, Jarineshin H, Malakshoar M. Effect of oral Tizanidine on postoperative pain herniorrhaphy. Journal of Medical Council of Iran 2017;35(2):167-74.
39. Taheri A, Hashemian M, Noroozi M, Bakhtiari M, Doroodian MR, Salajegheh S. Effect of oral tizanidine on prolongation of intrathecal lidocaine. J Emerg Prac Trauma 2018;4(2):62-6.
40. Hord A, Chalfoun AG, Denson D, Azevedo MI. Systemic tizanidine hydrochloride (zanafle™") relieves thermal hyperalgesia in rats with an experimental mononeuropathy. Anesth Analg 2001;93(5):1307-9.
41. de Santana Santos T, Calazans AC, Martins-Filho PR, Silva LC, de Oliveira ESED, Gomes AC. Evaluation of the muscle relaxant cyclobenzaprine after third-molar extraction. J Am Dent Assoc (1939) 2011;142(10):1154-62.
42. Gilron I. Review article: the role of anticonvulsant drugs in postoperative pain management: a bench-to-bedside perspective. Can J Anaesth 2006;53(6):562-71.
43. Beebe FA, Barkin RL, Barkin S. A clinical and pharmacologic review of skeletal muscle relaxants for musculoskeletal conditions. Am J Ther 2005;12(2):151-71.
44. Sibrack J, Hammer R. Methocarbamol. StatPearls. Treasure Island FL: © 2021, StatPearls Publishing LLC.; 2021.
45. Honda M, Sekiguchi Y, Sato N, Ono H. Involvement of imidazoline receptors in the centrally acting muscle-relaxant effects of tizanidine. Eur J Pharmacol 2002;445(3):187-93.
| Files | ||
| Issue | Vol 9, No 2 (Spring 2021) | |
| Section | Review Article(s) | |
| DOI | https://doi.org/10.18502/jpc.v9i2.6613 | |
| Keywords | ||
| Surgery; Postoperative Pain; Analgesia; Anticonvulsants; Muscle Relaxants | ||
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This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
How to Cite
1.
Jahani Sani S, Mashayekhi‐Sardoo H, Hosseinjani H. A Review of Studies on the Use of New Non-Gabapentinoid Anticonvulsants and Muscle Relaxants in the Control of Acute Postoperative Pain. J Pharm Care. 2021;9(2):96-105.
