Medscape is available in 5 Language Editions – Choose your Edition here.


Mononeuritis Multiplex Medication

  • Author: Divakara Kedlaya, MBBS; Chief Editor: Dean H Hommer, MD  more...
Updated: May 31, 2016

Medication Summary

The clinician must integrate the patient’s symptoms, signs, and clinical evaluation when considering the treatment of neuropathic pain in mononeuritis multiplex. The reduction of inflammation around the epineurium is the primary goal of treatment. Additional treatments are aimed at treating the primary cause and/or associated symptomology.

Over-the-counter analgesics are used for pain control. Various other medications may be used to reduce dysesthetic pain, which typically is a stabbing, burning pain.

Traditional medical models for treating chronic and neuropathic pain are based on the use of tricyclic antidepressants (eg, amitriptyline, nortriptyline, desipramine). When appropriate, anticonvulsant drugs have been used to treat lancinating pain. Gabapentin and pregabalin are medications of choice if tricyclic antidepressants are not effective. Despite its significant adverse effects profile, carbamazepine is the first-line medication for trigeminal neuralgia.

Advances in understanding of the pathophysiology of acute and chronic neuropathic pain states may lead to newer, more effective pharmacologic approaches to treatment.

More effective and safer antiepileptic drugs have continued to benefit patients with chronic pain conditions. Neurotransmitters such as serotonin, glutamate, substance P, calcitonin gene-related peptide (CGRP), and gamma-aminobutyric acid (GABA) are the targets of research and development of pharmacologic therapies for acute and chronic pain. In addition, sodium activity and calcium activity play important roles in the pathology and treatment of these chronic medical problems.

Medications that increase gastric motility (eg, metoclopramide) may be administered. Gastric motility also may be increased if the patient eats small, frequent meals and sleeps with his/her head elevated. Medications for bladder dysfunction include bethanechol and oxybutynin.

A report by Samson et al on two randomized, controlled trials indicated that in patients with eosinophilic granulomatosis with polyangiitis, non-hepatitis B virus polyarteritis nodosa, or microscopic polyangiitis (specifically, those patients whose five-factor score does not indicate a poor prognosis), the presence of mononeuritis multiplex can predict whether medical treatment other than corticosteroid therapy alone will be needed for a good outcome. The study involved 193 patients; 86 of them—as a result of corticosteroid failure, corticosteroid dependence, or relapse—required treatment in addition to corticosteroids (ie, intravenous immunoglobulins, biotherapies, cytotoxic agents, plasma exchanges). Univariate and multivariate analyses revealed that only the presence of initial mononeuritis multiplex was significantly associated with the need for add-on therapy.[55]


Opioid analgesics, including tramadol, have been found to be efficacious in several high-quality randomized controlled trials in patients with various types of neuropathic pain (grade A recommendation). However, owing to concerns over their long-term safety (relative to first-line medications), they are recommended principally for patients who have not responded to the first-line medications, except in certain clinical circumstances (ie, for the treatment of acute neuropathic pain, episodic exacerbations of severe neuropathic pain, neuropathic cancer pain, and during titration of a first-line medication when prompt relief of pain is needed).[56, 57]



Class Summary

These can be helpful if mononeuritis multiplex is associated with vasculitis. Failure to recognize and treat vasculitis can result in fatal consequences.[4, 5, 6]



Prednisone is an immunosuppressant used for the treatment of autoimmune disorders. It may decrease inflammation by reversing increased capillary permeability and suppressing polymorphonuclear leukocyte activity. The drug stabilizes lysosomal membranes and also suppresses lymphocytes and antibody production. Long-term treatment with corticosteroids may be necessary in individuals with mononeuritis multiplex.



Class Summary

If the overlying condition is inflammatory or autoimmune in nature, immunosuppressants may be of limited benefit to patients who are intolerant of steroids.

Intravenous immunoglobulin (IVIG; Carimune Gammagard S/D, Gamunex-C, Octagam)


Intravenous immunoglobulin (IVIG) uses anti-idiotypic antibodies to neutralize circulating myelin antibodies. IVIG down-regulates proinflammatory cytokines, including interferon-gamma. It blocks Fc receptors on macrophages, suppresses inducer T cells and B cells, and augments suppressor T cells. In addition, IVIG blocks complement cascade, promotes remyelination, and may increase cerebrospinal fluid (CSF) immunoglobulin G (10%).


Anticonvulsants, Other

Class Summary

These agents are used to treat associated symptoms of dysesthesia and neuropathic pain.

Gabapentin (Neurontin)


Gabapentin has anticonvulsant properties and antineuralgic effects; however, its exact mechanism of action is unknown. It is structurally related to GABA but does not interact with GABA receptors. Titration to effect can take place over several days (300 mg on day 1, 300 mg twice on day 2, and 300 mg 3 times on day 3).

Carbamazepine (Tegretol, Equetro, Epitol, Carbatrol)


Carbamazepine may reduce polysynaptic responses and block posttetanic potentiation. It is a first-line medication for trigeminal neuralgia.

Topiramate (Topamax)


Topiramate is a sulfamate-substituted monosaccharide with a broad spectrum of antiepileptic activity; it may have state-dependent sodium channel blocking action. It potentiates the inhibitory activity of the neurotransmitter GABA. In addition, topiramate may block glutamate activity. It is not necessary to monitor plasma concentrations of topiramate to optimize therapy. On occasion, the addition of topiramate to phenytoin may require adjustment of the phenytoin dose to achieve optimal clinical outcome.

Pregabalin (Lyrica)


Pregabalin is a structural derivative of GABA. Its mechanism of action is unknown. Pregabalin binds with high affinity to the alpha2-delta site (a calcium channel subunit). In vitro, it reduces the calcium-dependent release of several neurotransmitters, possibly by modulating calcium channel function. The US Food and Drug Administration (FDA) approved pregabalin for neuropathic pain associated with diabetic peripheral neuropathy or postherpetic neuralgia and as adjunctive therapy in partial-onset seizures.

Zonisamide (Zonegran)


Zonisamide is indicated for adjunctive treatment of partial seizures with or without secondary generalization. Evidence suggests that it is effective against myoclonic and other generalized seizure types.


Tricyclic Antidepressants

Class Summary

These agents have analgesic properties useful for chronic and neuropathic pain.



Amitriptyline inhibits the reuptake of serotonin and/or norepinephrine at the presynaptic neuronal membrane, which increases their concentration in the central nervous system (CNS). Amitriptyline may increase or prolong neuronal activity, since reuptake of these biogenic amines is important physiologically in terminating transmitting activity.

Imipramine (Tofranil)


These agents have been suggested to act by inhibiting reuptake of noradrenaline at synapses in central descending pain-modulating pathways located in the brainstem and spinal cord.

Nortriptyline (Pamelor)


Nortriptyline has demonstrated effectiveness in the treatment of chronic pain.

Desipramine (Norpramin)


This is the original TCA used for depression. These agents have been suggested to act by inhibiting reuptake of noradrenaline at synapses in central descending pain-modulating pathways located in the brainstem and spinal cord.


Prokinetic Agents

Class Summary

Medications that increase gastric motility (eg, Reglan) may be administered. Gastric motility also may be increased if the patient eats small, frequent meals and sleeps with his or her head elevated.

Metoclopramide (Reglan, Metozolv)


The antiemetic effect of metoclopramide appears to be due to its ability to block dopamine receptors in the chemoreceptor trigger zone (CTZ) of the central nervous system (CNS). This agent also enhances gastrointestinal motility and accelerates gastric emptying time.


Cholinergic Agonists

Class Summary

Medications for bladder dysfunction include bethanechol and oxybutynin.

Oxybutynin chloride (Ditropan IR, Ditropan XL, Gelnique)


Both the immediate-release and the extended-release forms of oxybutynin have both an anticholinergic and a direct smooth muscle relaxant effect on the urinary bladder. In addition, oxybutynin provides a local anesthetic effect on the irritable bladder.

The human detrusor has M2 and M3 muscarinic receptors. The M3 receptor mediates contractile response of the human detrusor. Oxybutynin has greater affinity for the M3 receptor. Urodynamic studies have shown oxybutynin increases bladder size, decreases frequency of symptoms, and delays initial desire to void.

Ditropan XL has an innovative drug delivery system: oral osmotic delivery system (OROS). The Ditropan XL tablet has a bilayer core that contains a drug layer and a "push layer" that contains osmotic components. The outer tablet is composed of a semipermeable membrane with a precision laser-drilled hole that allows the drug to be released at a constant rate.

When the drug is ingested, the aqueous environment in the gastrointestinal tract causes water to enter the tablet via the semipermeable membrane at a constant rate. The introduction of water inside the tablet liquefies drug and causes the push layer to swell osmotically. As the push layer swells, it forces the drug suspension out the hole at a constant rate over a 24-h period.

Ditropan XL achieves steady-state levels over a 24-h period. It avoids first pass metabolism in liver and upper gastrointestinal tract to avoid cytochrome P450 enzymes. It has excellent efficacy, with minimal adverse effects.

Bethanechol (Urecholine)


The stimulation of the parasympathetic nervous system by bethanechol increases bladder muscle tone, causing contractions that initiate urination.

Contributor Information and Disclosures

Divakara Kedlaya, MBBS Clinical Associate Professor, Department of Physical Medicine and Rehabilitation, Loma Linda University School of Medicine; Medical Director, Physical Medicine and Rehabilitation and Pain Management, St Mary Corwin Medical Center

Divakara Kedlaya, MBBS is a member of the following medical societies: American Academy of Physical Medicine and Rehabilitation, Colorado Medical Society, American Association of Neuromuscular and Electrodiagnostic Medicine

Disclosure: Nothing to disclose.

Chief Editor

Dean H Hommer, MD Chief, Department of Pain Management, Brooke Army Medical Center

Dean H Hommer, MD is a member of the following medical societies: American Academy of Medical Acupuncture, American Academy of Pain Medicine, American Academy of Physical Medicine and Rehabilitation, American Association of Neuromuscular and Electrodiagnostic Medicine, American College of Healthcare Executives, American College of Sports Medicine, American Institute of Ultrasound in Medicine, American Society of Interventional Pain Physicians, American Society of Regional Anesthesia and Pain Medicine

Disclosure: Nothing to disclose.


Paul V Brooks, MD Medical Director, Department of Physical Medicine and Rehabilitation, Lexington Clinic, PSC; Assistant Professor, Department of Orthopedics, Division of Sports Medicine, Assistant Professor, Department of Surgery, University of Kentucky College of Medicine

Paul V Brooks, MD is a member of the following medical societies: American Academy of Pain Medicine, American Academy of Physical Medicine and Rehabilitation, American Association of Neuromuscular and Electrodiagnostic Medicine, American Association of University Professors, American College of Sports Medicine, American Medical Association, American Pain Society, American Spinal Injury Association, Association for Academic Psychiatry, and Brain Injury Association of America

Disclosure: Nothing to disclose.

  1. Kelkar P, Parry GJ. Mononeuritis multiplex in diabetes mellitus: evidence for underlying immune pathogenesis. J Neurol Neurosurg Psychiatry. 2003 Jun. 74(6):803-6. [Medline]. [Full Text].

  2. Ryan MM, Tilton A, De Girolami U, Darras BT, Jones HR Jr. Paediatric mononeuritis multiplex: a report of three cases and review of the literature. Neuromuscul Disord. 2003 Nov. 13(9):751-6. [Medline].

  3. Parry GJ. Mononeuropathy multiplex (AAEE case report #11). Muscle Nerve. 1985 Jul-Aug. 8(6):493-8. [Medline].

  4. Bennett DL, Groves M, Blake J, et al. The use of nerve and muscle biopsy in the diagnosis of vasculitis: a 5 year retrospective study. J Neurol Neurosurg Psychiatry. 2008 Dec. 79(12):1376-81. [Medline]. [Full Text].

  5. Gorson KC. Vasculitic neuropathies: an update. Neurologist. 2007 Jan. 13(1):12-9. [Medline].

  6. Garzoni L, Vanoni F, Rizzi M, et al. Nervous system dysfunction in Henoch-Schonlein syndrome: systematic review of the literature. Rheumatology (Oxford). 2009 Dec. 48(12):1524-9. [Medline].

  7. Finsterer J. Systemic and non-systemic vasculitis affecting the peripheral nerves. Acta Neurol Belg. 2009 Jun. 109(2):100-13. [Medline].

  8. Tracy JA, Dyck PJ, Dyck PJ. Primary amyloidosis presenting as upper limb multiple mononeuropathies. Muscle Nerve. 2010 May. 41(5):710-5. [Medline]. [Full Text].

  9. Le Clech L, Rizcallah MJ, Alavi Z, Hutin P. Mononeuritis multiplex in a patient with B-cell prolymphocytic leukaemia: a diagnostic challenge. BMJ Case Rep. 2013 Sep 2. 2013:[Medline].

  10. Tomita M, Koike H, Kawagashira Y, Iijima M, Adachi H, Taguchi J, et al. Clinicopathological features of neuropathy associated with lymphoma. Brain. 2013 Aug. 136:2563-78. [Medline].

  11. Yamamoto T, Matsuda J, Kadoya H, Mori D, Ito D, Namba T, et al. A case of MPO-ANCA-positive polyarteritis nodosa complicated by exudative otitis media, mononeuritis multiplex, and acute renal failure. Clin Exp Nephrol. 2011 Oct. 15(5):754-60. [Medline].

  12. Makol A, Grover M. Adalimumab induced mononeuritis multiplex in a patient with refractory rheumatoid arthritis: a case report. Cases J. 2008 Oct 30. 1(1):287. [Medline]. [Full Text].

  13. Agarwal V, Singh R, Wiclaf, Chauhan S, Tahlan A, Ahuja CK, et al. A clinical, electrophysiological, and pathological study of neuropathy in rheumatoid arthritis. Clin Rheumatol. 2008 Jul. 27(7):841-4. [Medline].

  14. Florica B, Aghdassi E, Su J, Gladman DD, Urowitz MB, Fortin PR. Peripheral neuropathy in patients with systemic lupus erythematosus. Semin Arthritis Rheum. 2011 Oct. 41(2):203-11. [Medline].

  15. Bhowmik A, Banerjee P. Mononeuritis multiplex complicating systemic lupus erythematosus. Indian Pediatr. 2012 Jul. 49(7):581-2. [Medline].

  16. Martin AC, Friedlander M, Kiernan MC. Paraneoplastic mononeuritis multiplex in non-small-cell lung carcinoma. J Clin Neurosci. 2006 Jun. 13(5):595-8. [Medline].

  17. Leypoldt F, Friese MA, Böhm J, Bäumer T. Multiple enlarged nerves on neurosonography: an unusual paraneoplastic case. Muscle Nerve. 2011 May. 43(5):756-8. [Medline].

  18. Elamin M, Alderazi Y, Mullins G, Farrell MA, O'Connell S, Counihan TJ. Perineuritis in acute lyme neuroborreliosis. Muscle Nerve. 2009 Jun. 39(6):851-4. [Medline].

  19. Khadilkar SV, Benny R, Kasegaonkar PS. Proprioceptive loss in leprous neuropathy: a study of 19 patients. Neurol India. 2008 Oct-Dec. 56(4):450-5. [Medline]. [Full Text].

  20. Huda S, Krishnan A. An unusual cause of mononeuritis multiplex. Pract Neurol. 2013 Feb. 13(1):39-41. [Medline].

  21. Safadi R, Ben-Hur T, Shouval D. Mononeuritis multiplex: a rare complication of acute hepatitis A. Liver. 1996 Aug. 16(4):288-9. [Medline].

  22. Verma R, Lalla R, Babu S. Mononeuritis multiplex and painful ulcers as the initial manifestation of hepatitis B infection. BMJ Case Rep. 2013 May 2. 2013:[Medline].

  23. Santoro L, Manganelli F, Briani C, Giannini F, Benedetti L, Vitelli E, et al. Prevalence and characteristics of peripheral neuropathy in hepatitis C virus population. J Neurol Neurosurg Psychiatry. 2006 May. 77(5):626-9. [Medline]. [Full Text].

  24. Lenglet T, Haroche J, Schnuriger A, et al. Mononeuropathy multiplex associated with acute parvovirus B19 infection: characteristics, treatment and outcome. J Neurol. 2011 Jul. 258(7):1321-6. [Medline].

  25. Pai B S, Pai K. Livedoid Vasculopathy and Mononeuritis Multiplex, with a Fulminant Hepatic Failure which was caused by Herpes Simplex Hepatitis: A Case Report. J Clin Diagn Res. 2013 May. 7(5):921-3. [Medline]. [Full Text].

  26. Gabbai AA, Castelo A, Oliveira AS. HIV peripheral neuropathy. Handb Clin Neurol. 2013. 115:515-29. [Medline].

  27. Modi M, Vats AK, Prabhakar S, Singla V, Mishra S. Acro-osteolysis and mononeuritis multiplex as a presenting symptom of systemic angiitis of Wegener's type. Indian J Med Sci. 2007 Apr. 61(4):212-5. [Medline].

  28. Peshin R, O'Gradaigh D. Mononeuritis multiplex as a presenting feature of Wegener granulomatosis: a case report. Clin Rheumatol. 2007 Aug. 26(8):1389-90. [Medline].

  29. Campbell SB, Hawley CM, Staples C. Mononeuritis multiplex complicating Henoch-Schonlein purpura. Aust N Z J Med. 1994 Oct. 24(5):580. [Medline].

  30. Mori K, Iijima M, Koike H, Hattori N, Tanaka F, Watanabe H, et al. The wide spectrum of clinical manifestations in Sjögren's syndrome-associated neuropathy. Brain. 2005 Nov. 128:2518-34. [Medline].

  31. Pavlakis PP, Alexopoulos H, Kosmidis ML, Mamali I, Moutsopoulos HM, Tzioufas AG, et al. Peripheral neuropathies in Sjögren's syndrome: a critical update on clinical features and pathogenetic mechanisms. J Autoimmun. 2012 Aug. 39(1-2):27-33. [Medline].

  32. Takeuchi A, Kodama M, Takatsu M, Hashimoto T, Miyashita H. Mononeuritis multiplex in incomplete Behçet's disease: a case report and the review of the literature. Clin Rheumatol. 1989 Sep. 8(3):375-80. [Medline].

  33. Walker LJ, Swallow MW, Mirakhur M. Behçet's disease presenting with mononeuritis multiplex [corrected]. Ulster Med J. 1990 Oct. 59(2):206-10. [Medline]. [Full Text].

  34. Caselli RJ, Daube JR, Hunder GG, Whisnant JP. Peripheral neuropathic syndromes in giant cell (temporal) arteritis. Neurology. 1988 May. 38(5):685-9. [Medline].

  35. Lee P, Bruni J, Sukenik S. Neurological manifestations in systemic sclerosis (scleroderma). J Rheumatol. 1984 Aug. 11(4):480-3. [Medline].

  36. Mattie R, Irwin RW. Neurosarcoidosis Presenting as Mononeuritis Multiplex. Am J Phys Med Rehabil. 2013 Nov 5. [Medline].

  37. Garg S, Wright A, Reichwein R, Boyer P, Towfighi J, Kothari MJ. Mononeuritis multiplex secondary to sarcoidosis. Clin Neurol Neurosurg. 2005 Feb. 107(2):140-3. [Medline].

  38. Thawani SP, Brannagan TH 3rd, Lebwohl B, Green PH, Ludvigsson JF. Risk of Neuropathy Among 28,232 Patients With Biopsy-Verified Celiac Disease. JAMA Neurol. 2015 Jul. 72 (7):806-11. [Medline].

  39. Al-Shekhlee A, Katirji B. Sensory Mononeuropathy Multiplex in Chronic Graft versus Host Disease. J Clin Neuromuscul Dis. 2001 Jun. 2(4):184-6. [Medline].

  40. Grisold W, Piza-Katzer H, Jahn R, Herczeg E. Intraneural nerve metastasis with multiple mononeuropathies. J Peripher Nerv Syst. 2000 Sep. 5(3):163-7. [Medline].

  41. Wolf J, Bergner R, Mutallib S, Buggle F, Grau AJ. Neurologic complications of Churg-Strauss syndrome--a prospective monocentric study. Eur J Neurol. 2010 Apr. 17(4):582-8. [Medline].

  42. Hattori N, Ichimura M, Nagamatsu M, Li M, Yamamoto K, Kumazawa K, et al. Clinicopathological features of Churg-Strauss syndrome-associated neuropathy. Brain. 1999 Mar. 122 ( Pt 3):427-39. [Medline].

  43. Gemignani F, Brindani F, Alfieri S, Giuberti T, Allegri I, Ferrari C, et al. Clinical spectrum of cryoglobulinaemic neuropathy. J Neurol Neurosurg Psychiatry. 2005 Oct. 76(10):1410-4. [Medline]. [Full Text].

  44. Titlic M, Kodzoman K, Loncar D. Neurologic manifestations of hypereosinophilic syndrome--review of the literature. Acta Clin Croat. 2012 Mar. 51(1):65-9. [Medline].

  45. Isobe N, Kira J, Kawamura N, et al. Neural damage associated with atopic diathesis: a nationwide survey in Japan. Neurology. 2009 Sep 8. 73(10):790-7. [Medline].

  46. Greenberg MK, Sonoda T. Mononeuropathy multiplex complicating idiopathic thrombocytopenic purpura. Neurology. 1991 Sep. 41(9):1517-8. [Medline].

  47. Kumar S. Painful mononeuritis multiplex in idiopathic thrombocytopenic purpura. Indian Pediatr. 2005 Jun. 42(6):621-2. [Medline].

  48. Stafford CR, Bogdanoff BM, Green L, Spector HB. Mononeuropathy multiplex as a complication of amphetamine angiitis. Neurology. 1975 Jun. 25(6):570-2. [Medline].

  49. Burns TM, Shneker BF, Juel VC. Gasoline sniffing multifocal neuropathy. Pediatr Neurol. 2001 Nov. 25(5):419-21. [Medline].

  50. Sinha S, Mahadevan A, Lokesh L, Ashraf V, Chandrasekhar Sagar BK, Taly AB, et al. Tangier disease--a diagnostic challenge in countries endemic for leprosy. J Neurol Neurosurg Psychiatry. 2004 Feb. 75(2):301-4. [Medline]. [Full Text].

  51. Pollock M, Nukada H, Frith RW, Simcock JP, Allpress S. Peripheral neuropathy in Tangier disease. Brain. 1983 Dec. 106 ( Pt 4):911-28. [Medline].

  52. Mauermann ML, Ryan ML, Moon JS, et al. Case of mononeuritis multiplex onset with rituximab therapy for Waldenstrom's macroglobulinemia. J Neurol Sci. 2007 Sep 15. 260(1-2):240-3. [Medline].

  53. Said G, Lacroix-Ciaudo C, Fujimura H, et al. The peripheral neuropathy of necrotizing arteritis: a clinicopathological study. Ann Neurol. 1988 May. 23(5):461-5. [Medline].

  54. de Luna G, Chauveau D, Aniort J, et al. Plasma exchanges for the treatment of severe systemic necrotizing vasculitides in clinical daily practice: Data from the French Vasculitis Study Group. J Autoimmun. 2015 Dec. 65:49-55. [Medline].

  55. Samson M, Puéchal X, Devilliers H, et al. Mononeuritis multiplex predicts the need for immunosuppressive or immunomodulatory drugs for EGPA, PAN and MPA patients without poor-prognosis factors. Autoimmun Rev. 2014 Sep. 13(9):945-53. [Medline].

  56. O'Connor AB, Dworkin RH. Treatment of neuropathic pain: an overview of recent guidelines. Am J Med. 2009 Oct. 122(10 Suppl):S22-32. [Medline].

  57. Finnerup NB, Sindrup SH, Jensen TS. The evidence for pharmacological treatment of neuropathic pain. Pain. 2010 Sep. 150(3):573-81. [Medline].

All material on this website is protected by copyright, Copyright © 1994-2016 by WebMD LLC. This website also contains material copyrighted by 3rd parties.