Introduction
The most striking and alarming feature in patients with Guillain-Barré Syndrome (GBS) is progressive paralysis. Generally, less attention has been paid to pain, which may be a common and severe symptom in patients with GBS. Recognition of pain is very important, especially in patients unable to communicate due to intubation, because treatment against pain can be offered. Pain as a presenting symptom of GBS before the onset of weakness may be misleading in making the diagnosis of GBS and therefore can cause a delay in starting treatment for GBS.
Pain has been described in 3–89% of patients with GBS [
1,
6,
9,
14]. Different symptoms of pain associated with GBS have been distinguished: par-/dysaesthesiae, backache / root pain, meningism, muscle pain, joint pain, visceral pain and other types [
12]. One larger study in 55 GBS patients subdivided the different symptoms of pain as reported on admission into the following: low back pain with radiation (67.3%), dysaesthetic extremity pain (20%) and myalgic-rheumatic extremity pain (9.1%) [
9]. During the further non subdivided period of six months, low back pain with radiation (61.8%), dysaesthetic extremity pain (49.1%) and myalgic-rheumatic extremity pain (34.5%) were noted [
9]. As far as we know, there are no publications on the more detailed course and level of severity of the different pain symptoms during the first year after onset of GBS.
Pain in GBS can be very severe, and treatment is often far from successful. In some cases however a positive effect of treatment of pain in the acute phase has been described using corticosteroids [
8,
16]. The pathophysiology of pain is likely multifactorial. Increased endoneurial fluid pressure in nerve trunks possessing the epi- and perineurium may play a role [
2]. A possible cause of a salutary effect of corticosteroids could be a reduction of the perineurial and endoneurial inflammatory reaction in GBS.
Most reports on the effect of medication to relieve pain in GBS are based on limited numbers of patients. When measuring a treatment effect, often all types of pain are lumped together [
4,
8,
10,
11,
15‐
17]. Because it is likely that different pathophysiological mechanisms are related to these symptoms, a more detailed classification of different pain symptoms associated with GBS can be of help to study the effect of drugs.
This study focuses on the frequency, characteristics, severity and course of various symptoms of pain during the course of GBS and on the effect of methylprednisolone as was administered in a large placebo-controlled study.
Discussion
In this study, we prospectively investigated the frequency of pain and the effect of methylprednisolone on pain in a large group of GBS patients included in a randomized controlled trial. Retrospectively we investigated the frequency and course of the different symptoms of pain in more detail in a subgroup admitted to the coordinating center.
Pain appeared to be highly prevalent in this large, well documented group of GBS patients. 55% of these patients had pain at randomization. In other studies, the incidence of pain during the acute phase varies between 3% and 86% (median value 50%) [
1,
5‐
7,
9,
13,
14,
19,
20]. This variation mainly seems to be caused by the rather limited number of patients included in most studies.
It is remarkable that 70% of the patients reporting pain at randomization already had this pain prior to the onset of weakness. Pain as presenting symptom can lead to diagnostic difficulties [
3]. When pain initially is the only symptom, considering GBS as a possible diagnosis is not always so likely. So pain in the early phase can be confusing and later on may cause a delay in diagnosing and starting specific treatment for GBS. This is important to realize, because a delay in diagnosing GBS is potentially life threatening and may hamper recovery.
In the subgroup of patients that we investigated retrospectively in more detail, a somewhat higher percentage of patients (79%) reported pain in the acute phase compared to the whole group (55%). This is most likely due to the use of a time-interval of 2 weeks after randomization in stead of the fixed point in time at randomization.
In the randomized controlled trial, methylprednisolone was primarily evaluated in relation to the effect on disability of GBS [
18]. We did not use a clinimetrically validated scale to assess the level of severity of pain. Therefore the results of the effect of methylprednisolone on pain have to be interpreted with some caution. In the retrospective part of the study, we were able to assess the level of pain in more detail. We did this in relation to the use of analgesics. Because both treatment of GBS patients and treatment of pain is standardized in our center, it is likely that the prescription of analgesics is rather uniform and reported in a standardized way. This makes it rather well possible to judge about pain severity at a very global level in a retrospective way. It appeared that approximately a quarter of the GBS patients in this study reported extreme pain in the acute phase indicating that pain is not only a common but also a severe symptom.
Backache, interscapular and radicular pain were most frequently present in the acute phase. However painful par-/dysaesthesiae remained rather constantly present during at least one year (Table
3). This trend is comparable to findings in another larger study in which the different pain symptoms were noted on admission and during one further non subdivided period of 24 weeks [
9]. The pathophysiological explanation of pain in GBS is diverse. It seems that pain in the acute phase is predominantly nociceptive pain, due to inflammation of the nerve roots and peripheral nerves which may activate nociceptors. Later on, many GBS patients have neuropathic pain. This neuropathic pain is a non-nociceptive pain that doesn’t arise from pain receptors but results from degeneration and perhaps even regeneration of nerves and is often encountered in patients with chronic neuropathies. The persistence of muscle pain on the other hand may be related to more mechanical factors due to limitation of physical activities.
Previous case-reports suggest that corticosteroids might be an effective treatment for pain, possibly due to its anti-inflammatory effect [
8,
16]. This is the first study that evaluated the effect of methylprednisolone on pain in a placebo-controlled way. We did not find a significant decrease in the presence and severity of pain in the methylprednisolone treated group. This indicates that methylprednisolone for pain in general does not seem to have a positive effect. However, there are many symptoms of pain. In previous case reports, corticosteroids were reported to have a positive effect on radicular pain. In our series 10 out of 39 patients had radicular pain. All 5 patients treated with methylprednisolone, but also 4 out of 5 patients treated with placebo, had a decrease in severity of radicular pain after 4 weeks. The number of patients with radicular pain is too small to conclude about a possible favourable effect of methylprednisolone on this type of pain in GBS.
In conclusion, pain frequently occurs and may cause severe complaints in patients with GBS. It often starts before onset of weakness and therefore can lead to diagnostic difficulties. Most pain symptoms decrease within 2 weeks, but painful par-/dysaesthesiae and muscle pain may persist for months. Methylprednisolone seems to have no positive effect on the development and reduction of pain during the acute phase of GBS.