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• Pain in locked-in Guillain-Barré syndrome: pathophysiological and therapeutic thoughts
  JOSÉ BERCIANO
  Published on: 18 March 2022

• Published on: 18 March 2022

  Pain in locked-in Guillain-Barré syndrome: pathophysiological and therapeutic thoughts

  • JOSÉ BERCIANO, Professor emeritus ad honorem University of Cantabria, University Hospital “Marqués de Valdecilla (IDIVAL)”, and CIBERNED, Santander, Spain

  I read with great interest the excellent paper by Kumta and colleagues1 and the accompanying editorial2 concerning a patient with severe Guillain-Barré syndrome (GBS) requiring mechanical ventilation, who provided his experiences during the 31-day period of locked-in syndrome. I wish to open up some insights on the reported pain.
  Physical therapy, in particular the passive stretching of calf and masseter muscles, provoked him intense pain, the patient’s description being very impressive: “It felt like they were trying to tear the muscles off the bone … I’ve never known pain like it” 1. Pain due to peripheral nerve damage is basically divided into two major types: dysesthetic pain and nerve trunk pain, the distinction between them being based upon clinical observation and experience3. Reported aching characteristics in the current patient (excruciating, deep, and provoked by nerve stretch) points to nerve trunk pain.
  Pain is an integral manifestation of GBS. In a series of 55 consecutive GBS patients, Moulin and colleagues analysed pain features4, which could be summarised as follows: i/ 49 (89%) patients described pain during the course of their illness; ii/ in around half of them, it was described as excruciating; and iii/ pain preceded weakness by a mean of 5.3 days in 14, and both symptoms appeared simultaneously in seven. Furthermore, in “pure” motor GBS syndromes, usually classified as acute motor axonal neuropathy (AMAN), nerve trunk pain may occur in a h...

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  I read with great interest the excellent paper by Kumta and colleagues1 and the accompanying editorial2 concerning a patient with severe Guillain-Barré syndrome (GBS) requiring mechanical ventilation, who provided his experiences during the 31-day period of locked-in syndrome. I wish to open up some insights on the reported pain.
  Physical therapy, in particular the passive stretching of calf and masseter muscles, provoked him intense pain, the patient’s description being very impressive: “It felt like they were trying to tear the muscles off the bone … I’ve never known pain like it” 1. Pain due to peripheral nerve damage is basically divided into two major types: dysesthetic pain and nerve trunk pain, the distinction between them being based upon clinical observation and experience3. Reported aching characteristics in the current patient (excruciating, deep, and provoked by nerve stretch) points to nerve trunk pain.
  Pain is an integral manifestation of GBS. In a series of 55 consecutive GBS patients, Moulin and colleagues analysed pain features4, which could be summarised as follows: i/ 49 (89%) patients described pain during the course of their illness; ii/ in around half of them, it was described as excruciating; and iii/ pain preceded weakness by a mean of 5.3 days in 14, and both symptoms appeared simultaneously in seven. Furthermore, in “pure” motor GBS syndromes, usually classified as acute motor axonal neuropathy (AMAN), nerve trunk pain may occur in a high proportion of patients5, 6. In this regard, it is worth recalling that pain was an outstanding feature in the original AMAN description7: “many patients had neck and back stiffness and pain, one father said his son seemed as though he had a rod up his spine”. The corollary is that in any locked-in GBS, each healthcare assistant should assume the high likelihood of being confronted with a patient that may be suffering from nerve trunk pain, either spontaneous or provoked.
  The mechanism of pain in early stages of GBS (≤ 10 days after onset) is controversial4, 5; I shall offer a brief explanation. Pathological changes in early GBS mainly consist of inflammatory oedema predominating in the region where motor and sensory roots join to form spinal nerves8-10. Such lesional predominance is correlated with less efficient blood-nerve barrier of proximal nerve trunks9. Spinal roots traverse the subarachnoid space surrounded by an elastic multicellular root sheath derived from the arachnoid and penetrate the subarachnoid angle; external to this angle, the newly formed spinal nerves possess epi-perineurium and endoneurium as in the peripheral nerve trunks (see figure 3 in reference 9). The absence of epi-perineurium in the spinal roots probably prevents their having an increase of endoneurial fluid pressure (EFP) and ischemic injury despite inflammatory changes. Perineurium is relatively inelastic and has only a limited ability to expand9. Small increases of EFP, caused by endoneurial inflammation, can be accommodated, but any increase beyond these limits, as presumably occurs in early GBS, will produce an increase in EFP leading to compromise of transperineurial microcirculation and endoneurial ischemia, which causes proximal nerve conduction failure and eventually nerve trunk pain. In other words, in early severe GBS widespread inflammation of spinal nerves might account for neuropathic pain, indistinguishable from that associated with multilevel spinal root compression. In AMAN extension of ventral root inflammatory oedema into ventral rami of spinal nerves could involve abutting dorsal rami, thus causing nerve trunk pain referred to their innervation territories, from neck to buttocks, eventually accompanied by neck and back stiffness (masterfully illustrated in figure 1 of reference 7).
  Treatment of nerve trunk pain in GBS may be challenging, given that in addition to conventional non-steroidal anti-inflammatory drugs or simple analgesics, up to 74% of cases require opioids analgesics or even parental morphine9. The pathogenic role of inflammatory oedema in early GBS is the rationale for using short courses of intravenous corticosteroids; in fact, there have been at least 13 well-documented GBS patients with severe backache, unresponsive to analgesics, who exhibited rapid response to steroids9.
  The touching story of the current patient teaches us how distressing may be painful sensation in a patient suffering from locked-in GBS. As timely indicated by the authors, this calls for several approaches to minimize the “living nightmare”1. Concerning nerve trunk pain such approach should comprise the following measures: i/ optimal analgesic regimens including the potential use of short courses of intravenous corticosteroids; ii/ if the patient is not completely sedated, nerve traction maneuvers should be avoided during physical therapy; and iii/ whenever possible, approach the patient asking about pain.
   
  References
  1. Kumta N, Carter A, Schuller P, et al. Locked-in Guillain-Barré syndrome: 'my living nightmare'. Pract Neurol. Epub ahead of print: 2021 Oct 29:practneurol-2021-003110. doi: 10.1136/practneurol-2021-003110.
  2. Law D, Morgan M Listening to patients in intensive care. Epub ahead of print: Pract Neurol. 2021 Nov 29:practneurol-2021-003255. doi: 10.1136/practneurol-2021-003255.
  3. Asbury AK, Fields HL. Pain due to peripheral nerve damage: an hypothesis. Neurology 1984; 34: 1587-90.
  4. Moulin DE, Hagen N, Feasby TE, et al. Pain in Guillain-Barré syndrome. Neurology 1997; 48: 328-31.
  5. Ruts L, Rico R, van Koningsveld R, et al. Pain accompanies pure motor Guillain-Barré syndrome. J Peripher Nerv Syst 2008; 13: 305-6.
  6. Zhao F, Wang J, Zhang J, et al. Pain in acute motor axonal neuropathy. Muscle Nerve 2021; 64:739-43.
  7. McKhann GM, Cornblath DR, Ho T, et al. Clinical and electrophysiological aspects of acute paralytic disease of children and young adults in northern China. Lancet 1991; 338: 593-7.
  8. Haymaker WE, Kernohan JW. The Landry-Guillain-Barré syndrome; a clinicopathologic report of 50 fatal cases and a critique of the literature. Medicine (Baltimore) 1949; 28: 59-141.
  9. Berciano J, Sedano MJ, Pelayo-Negro AL, et al. Proximal nerve lesions in early Guillain-Barré syndrome: implications for pathogenesis and disease classification. J Neurol 2017; 264: 221-36.
  10. Berciano J. Axonal degeneration in Guillain-Barré syndrome: a reappraisal. J Neurol 2021; 268: 3728-43.

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  Conflict of Interest:
  None declared.

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