Zahid H. Bajwa

An association between migraine and cutaneous allodynia

Recent animal studies on the mechanism of migraine show that intracranial pain is accompanied by increased periorbital skin sensitivity. These findings suggest that the pathophysiology of migraine involves not only irritation of meningeal perivascular pain fibers but also a transient increase in the responsiveness (ie, sensitization) of central pain neurons that process information arising from intracranial structures and skin. The purpose of this study was to determine whether the increased skin sensitivity observed in animal also develops in humans during migraine attacks. Repeated measurements of mechanical and thermal pain thresholds of periorbital and forearm skin areas in the absence of, and during, migraine attacks enabled us to determine the occurrence of cutaneous allodynia during migraine. Cutaneous allodynia is pain resulting from a nonnoxious stimulus to normal skin. In 79% of the patients, migraine was associated with cutaneous allodynia as defined, and in 21% of the patients it was not. The cutaneous allodynia occurred either solely within the referred pain area on the ipsilateral head, or within and outside the ipsilateral head. Cutaneous allodynia in certain well‐defined regions of the skin during migraine is an as yet unreported neurological finding that points to hyperexcitability of a specific central pain pathway that subserves intracranial sensation. Ann Neurol 2000;47:614–624

Thalamic Sensitization Transforms Localized Pain into Widespread Allodynia

Focal somatic pain can evolve into widespread hypersensitivity to nonpainful and painful skin stimuli (allodynia and hyperalgesia, respectively). We hypothesized that transformation of headache into whole‐body allodynia/hyperalgesia during a migraine attack is mediated by sensitization of thalamic neurons that process converging sensory impulses from the cranial meninges and extracephalic skin.

Terminating Migraine With Allodynia and Ongoing Central Sensitization Using Parenteral Administration of COX1/COX2 Inhibitors

Objective.—To determine whether delayed infusion of COX1/COX2 inhibitors (ketorolac, indomethacin) will stop migraine in allodynic patients, and suppress ongoing sensitization in central trigeminovascular neurons in the rat.

tDCS-Induced Analgesia and Electrical Fields in Pain-Related Neural Networks in Chronic Migraine

Objective.— We investigated in a sham‐controlled trial the analgesic effects of a 4‐week treatment of transcranial direct current stimulation (tDCS) over the primary motor cortex in chronic migraine. In addition, using a high‐resolution tDCS computational model, we analyzed the current flow (electric field) through brain regions associated with pain perception and modulation.

Diagnosis and Treatment of Neuropathic Pain

Currently, no consensus on the optimal management of neuropathic pain exists and practices vary greatly worldwide. Possible explanations for this include difficulties in developing agreed diagnostic protocols and the coexistence of neuropathic, nociceptive and, occasionally, idiopathic pain in the same patient. Also, neuropathic pain has historically been classified according to its etiology (e.g., painful diabetic neuropathy, trigeminal neuralgia, spinal cord injury) without regard for the presumed mechanism(s) underlying the specific symptoms. A combined etiologic/mechanistic classification might improve neuropathic pain management. The treatment of neuropathic pain is largely empirical, often relying heavily on data from small, generally poorly-designed clinical trials or anecdotal evidence. Consequently, diverse treatments are used, including non-invasive drug therapies (antidepressants, antiepileptic drugs and membrane stabilizing drugs), invasive therapies (nerve blocks, ablative surgery), and alternative therapies (e.g., acupuncture). This article reviews the current and historical practices in the diagnosis and treatment of neuropathic pain, and focuses on the USA, Europe and Japan.

2003 Wolff Award: Possible parasympathetic contributions to peripheral and central sensitization during migraine.

Background.—Neurologic signs of increased parasympathetic outflow to the head often accompany migraine attacks. Because increased parasympathetic outflow to the cranial cavity induces vasodilation of cerebral and meningeal blood vessels, it can enhance plasma protein extravasation and the release of proinflammatory mediators that activate perivascular nociceptors. We recently showed that activation of intracranial perivascular nociceptors induces peripheral and central sensitization along the trigeminovascular pathway and proposed that these sensitizations mediate the intracranial hypersensitivity and the cutaneous allodynia of migraine.

Risk assessment of hemorrhagic complications associated with nonsteroidal antiinflammatory medications in ambulatory pain clinic patients undergoing epidural steroid injection.

We prospectively studied 1035 individuals undergoing 1214 epidural steroid injections to determine the risk of hemorrhagic complications. A history of bruising or bleeding was present in 176 (15%) patients. A platelet count was assessed in 77 patients before the epidural steroid injection; none was less than 100 × 109/L. Nonsteroidal antiinflammatory drugs (NSAIDs) were reported by 383 (32%) patients, including 34 patients on multiple medications. Aspirin was the most common NSAID and was noted by 158 patients, including 104 patients on 325 mg or less per day. There were no spinal hematomas (major hemorrhagic complications). Blood was noted during needle or catheter placement in 63 (5.2%) patients (minor hemorrhagic complications). NSAIDs did not increase the frequency of minor hemorrhagic complications. However, increased age, needle gauge, needle approach, needle insertion at multiple interspaces, number of needle passes, volume of injectant, and accidental dural puncture were all significant risk factors for minor hemorrhagic complications. There were 42 patients with new neurologic symptoms or worsening of preexisting complaints that persisted more than 24 h after injection; median duration of the symptoms was 3 days (range, 1–20 days). Our results confirm those of previous studies performed in obstetric and surgical populations that document the safety of neuraxial techniques in patients receiving NSAIDs. We conclude that epidural steroid injection is safe in patients receiving aspirin-like antiplatelet medications. Minor worsening of neurologic function may occur after epidural steroid injection and must be differentiated from etiologies requiring intervention.

Utilization patterns of tricyclic antidepressants in a multidisciplinary pain clinic: a survey.

OBJECTIVES Tricyclic antidepressants (TCA) have been shown to provide analgesia for a variety of neuropathic and headache pain syndromes regardless of the presence of depression. There is a high incidence of depression in patients with chronic pain, thereby making tricyclic antidepressants particularly suitable for chronic pain patients. We wanted to study patterns of use of tricyclic antidepressants in our Pain Management Center (Beth Israel Hospital, Boston, MA, U.S.A.) primarily to answer four questions: (1) What percentage of all patients were treated with tricyclic antidepressants? (2) How many patients were treated with each antidepressant, and what was the dose range used for individual antidepressants? (3) Were tricyclic antidepressants beneficial for chronic pain, and was that response dependent on a particular dose? (4) Did patients receive an adequate TCA trial, and what factors led to the discontinuation of a TCA trial? METHODS A total of 1,145 pain clinic patient charts were reviewed in alphabetical sequence. A total of 282 patients were identified as being treated with tricyclic antidepressants. Data were obtained from these 282 charts regarding the patients age, diagnosis, tricyclic antidepressant use and dose, other pain treatments, response to treatment, and side effects. The existing diagnosis of depression was documented if possible. Tricyclic antidepressant doses were defined as low doses when the equivalent of 50 mg or less of amitriptyline was used, and as full doses when the equivalent of at least 150 mg of amitriptyline was used. Response to treatment was noted as mild, moderate, or marked improvement. Patients reporting mild improvement were considered nonresponders. RESULTS Of 1,145 patients, 282 were treated with tricyclic antidepressants. A total of 205 (73%) of the patients were treated with low doses and only 34 (12%) with full doses. The remaining 43 (15%) received intermediate doses. Amitriptyline was the most commonly used drug (58%). Amitriptyline and doxepin appeared to be more effective than other tricyclic antidepressants. The rate of response to our treatment among the 31 patients with a coexisting diagnosis of depression was similar to the patients without documented depression. In patients with tricyclic antidepressants as the only treatment, there was only a trend toward greater response with full dose. In terms of side effects causing dose limitation or discontinuation of the drug, clomipramine, amitriptyline, and doxepin appeared to be worse than imipramine, desipramine, and nortriptyline. CONCLUSION Tricyclic antidepressants were used in 25% of patients referred to a multidisciplinary pain center and were commonly used in low to intermediate doses, even in situations in which there were neither side effects nor optimal clinical response.

Lack of Association Between Migraine Headache and Patent Foramen Ovale Results of a Case-Control Study

Background— Clinical observations of migraine headache symptoms in patients with a patent foramen ovale (PFO), both of which conditions are highly prevalent, have raised the question of a possible pathophysiological relationship. We sought to evaluate the assumption of an association between migraine headaches and the presence of PFO by use of a large case-control study. Methods and Results— We conducted a case-control study to assess the prevalence of PFO in subjects with and without migraine. Case subjects were those with a history of migraine (diagnosed by neurologists at a specialty academic headache clinic). Control subjects were healthy volunteers without migraine 1:1 matched on the basis of age and sex with case subjects. Presence of PFO was determined by transthoracic echocardiogram with second harmonic imaging and transcranial Doppler ultrasonography during a standardized procedure of infused agitated saline contrast with or without Valsalva maneuver and a review of the results by experts blinded to case-control status. PFO was considered present if both studies were positive. Odds ratios were calculated with conditional logistic regression in the matched cohort (n=288). In the matched analysis, the prevalence of PFO was similar in case and control subjects (26.4% versus 25.7%; odds ratio 1.04, 95% confidence interval 0.62 to 1.74, P=0.90). There was no difference in PFO prevalence in those with migraine with aura and those without (26.8% versus 26.1%; odds ratio 1.03, 95% confidence interval 0.48 to 2.21, P=0.93). Conclusions— We found no association between migraine headaches and the presence of PFO in this large case-control study.

Exploding vs. imploding headache in migraine prophylaxis with Botulinum Toxin A

&NA; Migraine headache is routinely managed using medications that abort attacks as they occur. An alternative approach to migraine management is based on prophylactic medications that reduce attack frequency. One approach has been based on local intramuscular injections of Botulinum Toxin Type A (BTX‐A). Here, we explored for neurological markers that might distinguish migraine patients who benefit from BTX‐A treatment (100 units divided into 21 injections sites across pericranial and neck muscles). Responders and non‐responders to BTX‐A treatment were compared prospectively (n = 27) and retrospectively (n = 36) for a host of neurological symptoms associated with their migraine. Data pooled from all 63 patients are summarized below. The number of migraine days per month dropped from 16.0 ± 1.7 before BTX‐A to 0.8 ± 0.3 after BTX‐A (down 95.3 ± 1.0%) in 39 responders, and remained unchanged (11.3 ± 1.9 vs. 11.7 ± 1.8) in 24 non‐responders. The prevalence of aura, photophobia, phonophobia, osmophobia, nausea, and throbbing was similar between responders and non‐responders. However, the two groups offered different accounts of their pain. Among non‐responders, 92% described a buildup of pressure inside their head (exploding headache). Among responders, 74% perceived their head to be crushed, clamped or stubbed by external forces (imploding headache), and 13% attested to an eye‐popping pain (ocular headache). The finding that exploding headache was impervious to extracranial BTX‐A injections is consistent with the prevailing view that migraine pain is mediated by intracranial innervation. The amenability of imploding and ocular headaches to BTX‐A treatment suggests that these types of migraine pain involve extracranial innervation as well.