G5 Artikkeliväitöskirja

Neural mechanisms of orofacial pain - effects of transcranial magnetic stimulation




TekijätLindholm Pauliina

KustantajaUniversity of Turku

KustannuspaikkaTurku

Julkaisuvuosi2017

ISBNISBN 978-951-29-6757-5

eISBNISBN 978-951-29-6758-2

Verkko-osoitehttp://urn.fi/URN:ISBN:978-951-29-6758-2

Rinnakkaistallenteen osoitehttp://urn.fi/URN:ISBN:978-951-29-6758-2


Tiivistelmä

Neuropathic orofacial pain is challenging to treat. Limited knowledge of the underlying pain-syndrome-specific pathophysiology is one of the reasons for poor response to current pharmacotherapy. Patients with treatment-resistant neuropathic pain are susceptible to concomitant psychiatric and sleep disorders. Psychiatric disorders, sleep problems, and certain personality traits may, in turn, predispose to chronic pain. Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive neuromodulation technique that has been shown to alleviate neuropathic pain, but the mechanisms of its action and optimal treatment parameters are still unclear. 

We investigated rTMS effects in healthy subjects and chronic neuropathic orofacial pain patients, and compared the analgesic efficacy of stimulation given to different cortical targets. We also evaluated the brain mechanisms involved in rTMS-induced analgesia, especially the dopamine-opioid system. The genetically determined function of the endogenous dopamine system was also investigated regarding thermal and pain perception. 

We discovered that rTMS targeted to the right secondary somatosensory cortex (S2) alleviated neuropathic orofacial pain (Cohen’s d = 0.60). Pain intensity assessed in numerical rating scale was significantly lower after the S2 stimulation than after the stimulation of the primary somatosensory and motor cortex (S1/M1) (p = 0.007) or placebo (p = 0.019). The analgesic effect of stimulation of the S2 region was not mediated or predicted by comorbid psychiatric or sleep disorders. Orofacial pain patients had more psychiatric and sleep disorders than the general population and there were several associations between these comorbid disorders. 

The variation caused by single nucleotide polymorphism 957C>T in dopamine receptor D2 (DRD2) gene had an effect on thermal perception and rTMS effects in healthy subjects. rTMS to S1 cortex increased heat pain detection thresholds only in subjects homozygous for the 957T allele (F = 3.78, p = 0.009), whose mean heat pain detection thresholds 6,24 were initially lower than those of 957C allele carriers (p < 0.05). The “pain sensitive” 957TT genotype was overrepresented (50% vs. 27% in general population, p = 0.019) in our unselected group of neuropathic pain patients. 

In the positron emission tomography (PET) study on healthy subjects, lower μ-opioid receptor availability indicting activation of the endogenous opioid system, was seen in a brain network associated with pain processing after active S1/M1 rTMS compared to sham (p ≤ 0.0001). 

Our results suggest that the brain dopamine-opioid system is important in the perception and modulation of pain, and in rTMS-induced analgesia. Genetic regulation of striatal DRD2 function may explain some of the individual differences in pain sensitivity and in risk for neuropathic pain.



Last updated on 2024-03-12 at 13:20