| Summary: | 博士 === 國立陽明大學 === 神經科學研究所 === 104 === Pain is a universal experience that could be physiological or pathological. Physiological pain is a vital function in the survival of almost any individuals. On the other hand, pathological pain is a group of pandemic disorders involving almost every parts of our body. According to the Global Burden of Disease Survey 2010 conducted by World Health Organization (WHO), tension-type headache, migraine and low back pain rank the top ten most prevalent diseases of the human kind. These pain disorders are episodic in nature, but they could be chronic and thus more disabling. The mechanisms of how acute and physiological pain turns into a chronic and pathological condition are important issues in the research fields of pain.
Migraine is a common pain disorder characterized by unilateral and throbbing headache with moderate to severe intensity and aggravation by physical activity. Associated features include nausea, vomiting, phonophobia, photophobia, and so on. While most patients with migraine have episodic attacks (i.e. episodic migraine, EM), some of them may have chronic migraine (CM), defined as headache frequency ≥ 15 days per month, for more than three months. Though the mechanisms responsible for the transformation remains speculative, the dysfunctions in endogenous pain modulation, central sensitization and medication overuse (MO) have been proposed. Medication overuse is defined as using analgesics for ≥ 10 or 15 days per month, for more than 3 months. It has been reported that about half patients with CM have concomitant MO.
At first, we tried to explore the possible dysfunction of endogenous pain modulation in patients with migraine. We aimed to investigate the 1H- magnetic resonance spectroscopy (MRS) metabolite ratios at the periaqueductal gray and bilateral dorsal pons, the areas known to play important roles in the pain modulation. A total of 19 patients with EM, 53 patients with CM (with MO n = 30, without MO n = 23) and 16 control subjects completed the study. Patients with EM had the highest N-acetylaspartate (NAA)/creatine (Cr) ratio at the dorsal pons (right, P = 0.014; left, P = 0.034) in comparison with those with CM and controls. Among migraine patients, NAA/Cr ratios at dorsal pons were inversely correlated with headache frequency (right, r = -0.350, P = 0.004; left, r = -0.284, P = 0.019) and intensity (right, r = -0.286, P = 0.019; left, r = -0.244, P =0.045). Of note, MO was not associated with brainstem MRS ratios in patients with CM. The increased NAA/Cr levels may suggest neuronal hypertrophy at the dorsal pons in patients with EM. We proposed a progressive dysfunction of this region may occur during the transformation from EM to CM since the NAA/Cr levels declined with increasing headache frequency and intensity.
Based on the previous study, we further tried to explore the neural plasticity changes associated with migraine in a whole brain range. We conducted another brain magnetic resonance imaging (MRI) study analyzed by voxel-based morphometry. A total of 66 patients with CM (half with MO), 33 patients with EM and 33 controls completed the study. Gray matter volume (GMV) loss was noted in patients with migraine, as compared with controls. The involved brain regions were compatible with the so-called “pain matrix” brain areas. We further tested the effect of MO in patients with CM and the result showed GMV decrease in the orbitofrontal cortex and left middle occipital gyrus as well as a GMV increase in the left temporal pole/parahippocampus. The GMV changes explained 31.1% variance of the analgesics use frequency. The patients who responded to treatment had a greater GMV in the orbitofrontal cortex (P = 0.028).
In conclusion, our study showed different forms of neural plasticity changes associated with migraine and its chronification. These findings may help in understanding the effect of migraine to the brain that may be extrapolated to chronic pain, though differences may exist in different types of pain disorders.
|
|---|
