Korean J Pain.  2016 Jan;29(1):40-47. 10.3344/kjp.2016.29.1.40.

Nefopam Reduces Dysesthesia after Percutaneous Endoscopic Lumbar Discectomy

• Ok YM
• Cheon JH
• Choi EJ
• Chang EJ
• Lee HM
• Kim KH

• KMID: 2151659
• DOI: http://doi.org/10.3344/kjp.2016.29.1.40

Abstract

BACKGROUND
Neuropathic pain, including paresthesia/dysesthesia in the lower extremities, always develops and remains for at least one month, to variable degrees, after percutaneous endoscopic lumbar discectomy (PELD). The recently discovered dual analgesic mechanisms of action, similar to those of antidepressants and anticonvulsants, enable nefopam (NFP) to treat neuropathic pain. This study was performed to determine whether NFP might reduce the neuropathic pain component of postoperative pain.
METHODS
Eighty patients, who underwent PELD due to herniated nucleus pulposus (HNP) at L4-L5, were randomly divided into two equal groups, one receiving NFP (with a mixture of morphine and ketorolac) and the other normal saline (NS) with the same mixture. The number of bolus infusions and the infused volume for 3 days were compared in both groups. The adverse reactions (ADRs) in both groups were recorded and compared. The neuropathic pain symptom inventory (NPSI) score was compared in both groups on postoperative days 1, 3, 7, 30, 60, and 90.
RESULTS
The mean attempted number of bolus infusions, and effective infused bolus volume for 3 days was lower in the NFP group for 3 days. The most commonly reported ADRs were nausea, dizziness, and somnolence, in order of frequency in the NFP group. The median NPSI score, and all 5 median sub-scores in the NFP group, were significantly lower than that of the NS group until postoperative day 30.
CONCLUSIONS
NFP significantly reduced the neuropathic pain component, including paresthesia/dysesthesia until 1 month after PELD. The common ADRs were nausea, dizziness, somnolence, and ataxia.

Keyword

Adverse drug reactions; Dysesthesia; Herniated discs; Intravenous infusion; Nefopam; Neuropathic pain; Percutaneous discectomy; Postoperative pain; Symptom assessment

MeSH Terms

Anticonvulsants
Antidepressive Agents
Ataxia
Diskectomy*
Diskectomy, Percutaneous
Dizziness
Drug-Related Side Effects and Adverse Reactions
Humans
Infusions, Intravenous
Intervertebral Disc Displacement
Lower Extremity
Morphine
Nausea
Nefopam*
Neuralgia
Pain, Postoperative
Paresthesia*
Symptom Assessment
Anticonvulsants
Antidepressive Agents
Morphine
Nefopam

Figure

• 

  Fig. 1 A flow chart. All 80 participants, who were to receive percutaneous endoscopic lumbar discectomy (PELD) at L4-L5, had already completed basic laboratory examination, including a complete blood count, liver and renal function tests, and electrolyte level tests before hospitalization. They randomly received a mixture of 15 mg of morphine and 270 mg of ketorolac with or without 180 mg of nefopam (NFP) (the NFP group or NS group) using a postoperative intravenous patient-controlled analgesia (PCA) device. The PCA use began with an infusion just before the operation, without a loading dose. The PCA was programmed for a total volume of 100 ml with a basal infusion rate of 1 ml/h, a bolus infusion volume of 1 ml, with a lockout interval of 1 hour without a 4 hour volume limit, for 3 days. The mean attempted number of bolus infusions, and effective infused bolus volume for 3 days were compared in both groups. The adverse reactions in both groups were also recorded and compared.

• 

  Fig. 2 The median scores of the grades by the duration of spontaneous pain (SP) and the number of pain attacks (PA) during the study days. The grades by the duration of SP during the past 24 h was lower, and the grades by the number of PA during the past 24 h was lower in the nefopam (NFP) group from the postoperative day 1 to 30 (P < 0.05). NFP: nefopam, NS: normal saline, Grades by duration of SP: grade 1 (less than 1 h), grade 2 (between 1 and 3 h), grade 3 (between 4 and 7 h), grade 4 (8 and 12 h), and grade 5 (permanently), Grades by frequency of PA: grade 0 (no pain attack), grade 1 (between 1 and 5), grade 2 (between 6 and 10), grade 3 (between 11 and 20), and grade 4 (more than 20).

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  Fig. 3 Adverse reactions. The most commonly reported adverse reactions during the administration of patient-controlled analgesia for the postoperative 3 days were nausea, dizziness, somnolence, and ataxia, in order of frequency in both groups. Nausea in the NFP group was more frequent than that of the normal saline (NS) group (P < 0.05).

Reference

1. Kim KH. Use of lidocaine patch for percutaneous endoscopic lumbar discectomy. Korean J Pain. 2011; 24:74–80. PMID: 21716614.

2. Cho JY, Lee SH, Lee HY. Prevention of development of postoperative dysesthesia in transforaminal percutaneous endoscopic lumbar discectomy for intracanalicular lumbar disc herniation: floating retraction technique. Minim Invasive Neurosurg. 2011; 54:214–218. PMID: 22287030.

3. Loeser JD. Pain of neurologic origin in the hips and lower extremities. In : Loeser JD, Bonica JJ, editors. Bonica's management of pain. 3rd ed. Philadelphia (PA): Lippincott Williams & Wilkins;2001. p. 1565–1578.

4. Gregori-Puigjané E, Setola V, Hert J, Crews BA, Irwin JJ, Lounkine E, et al. Identifying mechanism-of-action targets for drugs and probes. Proc Natl Acad Sci U S A. 2012; 109:11178–11183. PMID: 22711801.

5. Moore RA, Derry S, McQuay HJ, Wiffen PJ. Single dose oral analgesics for acute postoperative pain in adults. Cochrane Database Syst Rev. 2011; CD008659. PMID: 21901726.

6. Alfonsi P, Adam F, Passard A, Guignard B, Sessler DI, Chauvin M. Nefopam, a nonsedative benzoxazocine analgesic, selectively reduces the shivering threshold in unanesthetized subjects. Anesthesiology. 2004; 100:37–43. PMID: 14695722.

7. Heel RC, Brogden RN, Pakes GE, Speight TM, Avery GS. Nefopam: a review of its pharmacological properties and therapeutic efficacy. Drugs. 1980; 19:249–267. PMID: 6991238.

8. Podranski T, Bouillon TW, Riva T, Kurz AM, Oehmke MJ. Compartmental pharmacokinetics of nefopam during mild hypothermia. Br J Anaesth. 2012; 108:784–791. PMID: 22331396.

9. Bouhassira D, Attal N, Fermanian J, Alchaar H, Gautron M, Masquelier E, et al. Development and validation of the Neuropathic Pain Symptom Inventory. Pain. 2004; 108:248–257. PMID: 15030944.

10. Czuczwar M, Czuczwar K, Cięszczyk J, Kiś J, Saran T, Łuszczki JJ, et al. Nefopam enhances the protective activity of antiepileptics against maximal electroshock-induced convulsions in mice. Pharmacol Rep. 2011; 63:690–696. PMID: 21857079.

11. Novelli A, Groppetti A, Rossoni G, Manfredi B, Ferrero-Gutiérrez A, Pérez-Gómez A, et al. Nefopam is more potent than carbamazepine for neuroprotection against veratridine in vitro and has anticonvulsant properties against both electrical and chemical stimulation. Amino Acids. 2007; 32:323–332. PMID: 17021653.

12. Novelli A, Díaz-Trelles R, Groppetti A, Fernández-Sánchez MT. Nefopam inhibits calcium influx, cGMP formation, and NMDA receptor-dependent neurotoxicity following activation of voltage sensitive calcium channels. Amino Acids. 2005; 28:183–191. PMID: 15714253.

13. Verleye M, André N, Heulard I, Gillardin JM. Nefopam blocks voltage-sensitive sodium channels and modulates glutamatergic transmission in rodents. Brain Res. 2004; 1013:249–255. PMID: 15193535.

14. Kim KH, Abdi S. Rediscovery of nefopam for the treatment of neuropathic pain. Korean J Pain. 2014; 27:103–111. PMID: 24748937.

15. Sittl R, Irnich D, Lang PM. Update on preemptive analgesia: options and limits of preoperative pain therapy. Anaesthesist. 2013; 62:789–796. PMID: 24052051.

16. Choi I, Ahn JO, So WS, Lee SJ, Choi IJ, Kim H. Exiting root injury in transforaminal endoscopic discectomy: preoperative image considerations for safety. Eur Spine J. 2013; 22:2481–2487. PMID: 23754603.

17. Durrieu G, Olivier P, Bagheri H, Montastruc JL;. Overview of adverse reactions to nefopam: an analysis of the French Pharmacovigilance database. Fundam Clin Pharmacol. 2007; 21:555–558. PMID: 17868209.

18. Haroutiunian S, Nikolajsen L, Finnerup NB, Jensen TS. The neuropathic component in persistent postsurgical pain: a systematic literature review. Pain. 2013; 154:95–102. PMID: 23273105.

19. Joo YC, Ko ES, Cho JG, Ok YM, Jung GY, Kim KH. Intravenous nefopam reduces postherpetic neuralgia during the titration of oral medications. Korean J Pain. 2014; 27:54–62. PMID: 24478902.