Abstract
Cephalic and extracephalic allodynia are recognized as a common sign of sensory sensitization during migraine episodes. However, the occurrence of body pain in migraine has not been thoroughly explored. Here we report three patients presenting with spontaneous body pain in association with migraine attacks. A 41-year-old woman experienced face and limb pain along with migraine headaches; it started before, during or after headache, was usually ipsilateral to head pain, and could last from minutes to days. A 39-year-old woman had pain in her right limbs, back and neck for 30-60 min prior to right-sided migraine headaches. A 30-year-old woman perceived pain in her left upper limb for 24-48 h prior to left-sided migraine headaches. All patients had allodynia to mechanical stimuli over the painful areas. Spontaneous body pain may be associated with migraine attacks. Together with allodynia, this might be a consequence of central sensitization.
Introduction
Migraine symptoms are known to include more than just head pain. For example, cephalic and extracephalic allodynia are currently recognized as a common sign of sensory sensitization during migraine episodes (1–7). However, the occurrence of spontaneous body pain is not included in standard migraine descriptions, and has only rarely been reported (8–10). Here we describe the clinical features of three patients presenting with recurrent attacks of non-headache pain in close temporal relationship with migraine headaches.
Case reports
Patient 1
A 41-year-old woman had suffered from migraine headaches since the age of 27 years. Head pain was usually right-sided, but occasionally became bilateral. The headaches were pulsating, moderately to severely intense, associated with photophobia, phonophobia and nausea, and commonly preceded or accompanied by typical aura symptoms including photopsias, scotomas, cheiro-oral paraesthesias or dysphasic speech. If untreated, the headache lasted for several hours, but was usually responsive to analgesics, non-steroidal anti-inflammatory drugs (NSAIDs) or triptans. The attack frequency varied, but over the last year it had exceeded 15 days per month without medication overuse, fulfilling criteria of chronic migraine.
Two years after her migraines had begun, she had started having numerous attacks of facial and body pain in connection with headache episodes. Pain could be located in different anatomical regions, and was much more common on the right (Fig. 1). At times it was first perceived in a restricted area (e.g. right V-2 territory or right hand) and could either stay confined or gradually extend to wider areas (e.g. the right hemifacies or even the whole right side of the body). On some occasions it started on the right side and finally spread to the left side, frequently affecting different body regions in an erratic way. It usually had a tightening or burning quality, but there could be superimposed paroxysms of lancinating pain resembling neuralgia or radiculopathy. Sometimes the extracephalic pain had a throbbing character, and this could coexist with a pulsating ipsilateral hemicrania. The intensity of facial and limb pain typically ranged from 2 to 4, but could reach 7 on a 10-point visual analogue scale. Limb movements and deep pressure increased pain intensity in the affected regions, and there could be cutaneous allodynia in a particular painful area so that light touch or wind exposure could provoke pain. These sensations often preceded migraine headache for minutes to hours, sometimes overlapping with the visual aura, but would occasionally start in unison or follow headache onset. The duration of face or limb pain was quite irregular, extending from 5 min to several hours. When the headaches were more frequent it could wax and wane for as long as 1 week. No symptomatic medications for headaches, including triptans, had any effect on the pain outside the head. However, both amitryptiline (25 mg per day) and topiramate (100 mg per day) at different periods significantly reduced both migraine headache and the abnormal body sensations.
Body regions that could be painful in association with migraine attacks in each patient (dark shaded: frequently affected; light shaded: seldom affected).
During low-grade right face and right limb pain with a score around 2 out of 10, patchy cutaneous allodynia was found over the most painful areas. The patient was tested for both static and dynamic mechanical allodynia with a previously established procedure (11). In the most affected areas static pressure with Von Frey filaments of 1.4, 8 and 60 g evoked slight to moderate unpleasant sensations (3–5 on a 10-point scale), and brush stimuli with a folded gauze was moderately to extremely disturbing (4–8 on a 10-point scale). The same stimuli were not noxious when applied over symmetrical body regions. In addition, quantitative sensory testing demonstrated an asymmetric thermal sensitivity. A 25 × 50-mm thermode (Somedic, Stockholm, Sweden) was attached to each hand while the right upper limb was slightly painful (2 out of 10). Thermal sensory thresholds were measured using the method of limits (12, 13). With a baseline temperature of 32°C, the skin was cooled down and warmed up until cold or heat was perceived, at which moment the patient pressed a button and stopped the stimulus. Both tests were repeated five times on each side, and the mean temperature changes for cold and heat perception were lower on the right (thresholds for cold: 30.1 ± 0.36°C on the right vs. 27.0 ± 0.68°C on the left; thresholds for heat: 34.6 ± 0.30°C on the right vs. 36.8 ± 0.65°C on the left). Otherwise no neurological deficits were detected. An EEG and magnetic resonance imaging (MRI) of the brain were normal.
Patient 2
A 39-year-old woman had had migraine headaches since the age of 15 years. Headache was always unilateral, more often right-sided, and was a moderate or severe pulsating pain that increased with physical activity, with associated photophobia, phonophobia, nausea and vomiting. Head pain was occasionally preceded or accompanied by visual aura (flickering lines or spots). The headache lasted up to 3 days if untreated, but usually disappeared with ergots, whereas NSAIDs or triptans were partially or completely effective. Headaches occurred two to three times per month. The patient had never been treated with a migraine preventive.
At age 34 years, the patient had begun to experience body pain in association with most migraine episodes. Prior to headache onset, she developed an aching sensation in one of her right extremities. It usually started in the ulnar region of her right hand and progressed upwards until it reached the right side of the back over the scapula and the neck. Sometimes it started more proximally and was confined to the right shoulder and the right side of the back. Less frequently it was located over her right knee and right thigh (Fig. 1). This sensation was described as a low-grade pain (2–3 out of 10) with a tightening or burning character that intermittently became throbbing. With this spontaneous discomfort, there was increased sensitivity on the right side of the body. Combing her hair, being exposed to wind, and wearing eyeglasses, earrings or tight clothes could precipitate unpleasant sensations. Both right-sided body pain and allodynia preceded headache for 30–60 min. Body pain could either stop or continue with migraine headache, whereas the allodynia usually outlasted the headache. There was no relief of these symptoms with any analgesic or acute migraine medication.
Four days after her last migraine attack, the patient had a normal examination except for pressure allodynia on her right hand and forearm. Von Frey hairs of 1.4, 8 and 60 g evoked pain with scores of 6, 8 and 9 on a 10-point scale, respectively. No pain was elicited over the corresponding areas on the left side. Intracranial and cervical lesions were ruled out with MRI.
Patient 3
A 30-year-old woman had suffered from migraine headaches since the age of 23 years. Head pain was always located on the left frontotemporal region, had a pulsating character, was very intense and incapacitating, and increased with head movements. There were nausea, vomiting, photophobia and phonophobia, but no typical aura symptoms. If untreated, headache could continue for up to 3 days and recurred with a frequency of one to three attacks per month. Treatment with triptans was generally successful, whereas NSAIDs were only partially effective. She had never been on migraine prophylactic therapy.
Since onset, headache attacks were mostly preceded by a low-grade ache in her left upper limb (Fig. 1), with pain intensity score around 2 out of 10. The pain was perceived as a heavy or pressing sensation, most severe in the arm, and could occasionally be accompanied by allodynia with light touch to the painful area. These symptoms always started 24–48 h prior to headache. The pain normally disappeared soon after head pain began, but the allodynia could persist on the left side of her head and body during headache attacks. She had not tried any medications to alleviate the arm pain.
Six days after her last migraine attack no neurological signs were detected except for asymmetric sensitivity to pressure stimuli over her upper limbs. Von Frey filaments of 8 g and 60 g repeatedly evoked unpleasant sensations (1–2 points on a 10-point scale) on the lateral aspect of the left arm, but not in any region of the contralateral arm. MRIs of the brain and the cervical spine were normal.
Discussion
Migraine may have a variety of symptoms including atypical pain. Some non-headache pain conditions have been related to migraine. Such is the case of abdominal migraine, an episodic abdominal pain that is seen mainly in children as a precursor of migraine (14). Some episodes of recurrent limb pain in childhood might also be connected to migraine (15, 16). A probable migrainous equivalent has been described in a headache patient presenting with recurrent pain over the head, limbs and trunk that improved with migraine therapy (17). In addition, some studies indicate that migraine frequently coexists with fibromyalgia (18, 19). However, body pain as a migrainous accompaniment has not been widely recognized.
After some scarce references in the past (9), 10 cases of limb pain concomitant with migraine headache were reported by Guiloff and Fruns in 1988 (8), and 10 additional cases were communicated by Raudino in 1994 (10). The limb pain usually started during the headache and only preceded headache in a single case of Raudino's series. Otherwise, there are important similarities between these former cases and our patients. The main features of the three series are shown in Table 1. We do not know the prevalence of extracephalic pain associated with migraine attacks, but it is probably low. Among 152 migraineurs, from a total of 245 headache patients, Raudino found 10 patients with migrainous limb pain from a total of 11 patients with limb pain and headache (10). Since few cases have been described, little can be said about therapy. Analgesics or acute migraine medications improved limb pain in a small number of patients of previous series, but did not have the same effect in any of our patients. On the other hand, migraine preventives were usually successful in Guiloff's cases (8), and our first patient also found significant relief with amitryptiline and topiramate.
Main features of patients with body pain associated with migraine attacks in recent series
Guiloff's series had both migraine and cluster headache patients (n = 22). Body pain never preceded headache and was usually concomitant with either migraine or cluster headache attacks. Limb pain started after head pain in a single case, but the headache diagnosis was not specified.
MA, Migraine with aura; MoA, migraine without aura.
Recently, much interest has been focused on the emergence of cephalic and extracephalic cutaneous allodynia during migraine attacks (1, 3, 4, 7). A temporal sequence has been described, with allodynia appearing approximately 1 h after the onset of head pain, lasting the duration of headache or longer (2, 3). Burstein has proposed that these events are probably due to the development of central sensitization involving second-order neurons in the trigeminal nucleus, which receive convergent information from the meninges, the scalp and the face, and at least third-order neurons in the thalamus, which process information from the whole body (1, 2, 20).
Sensory sensitization can provoke not only allodynia and hyperalgesia, but also spontaneous pain (21, 22). Our patients had spontaneous body pain associated with their migraine attacks, and this may be another consequence of central sensitization. In fact, they also showed allodynia to mechanical stimuli over the painful areas. Spontaneous pain may indicate that these patients had a higher degree of sensory sensitization than most migraine patients. On the other hand, such body sensations were early phenomena in our patients: they consistently preceded headache in patients 2 and 3, and usually started prior to headache in patient 1. This suggests that a symptom generator for body pain with allodynia may become active before, during or, as in the previously reported cases, after the onset of the headache. Other non-headache symptoms such as weariness, mood changes, hunger, thirst, photophobia, phonophobia or nausea may precede, accompany or follow migraine head pain (23).
In conclusion, migrainous corpalgia may be considered a migraine variant or a migraine manifestation, and it may have a variable temporal relationship to migraine head pain. The potential association of body pain and/or allodynia may have major implications for our understanding of migraine pathophysiology. Migraine may be not only a headache disorder but also a generalized disorder of nociception.