Journal of Headache and Pain最新文献

Background: Body pain significantly affects the quality of life. However, the relationship between headache and pain across broad body regions remains unclear. This population-based cross-sectional study aimed to investigate the prevalence and impact of body pain in migraine and tension-type headache (TTH).

Methods: We analyzed baseline data from 2,548 participants in the Korean population-based Circannual Change in Headache and Sleep study. Participants were classified into migraine (n = 145), TTH (n = 805), and no-headache (n = 920) groups. Body pain was assessed across 19 regions using the Widespread Pain Index (WPI). Multivariable analyses adjusted for age, sex, and psychiatric symptoms were performed.

Results: Body pain was more widespread in the migraine and TTH than in the no-headache group, showing a gradient of migraine > TTH > no-headache (P < 0.001). Migraine was most strongly associated with neck pain (odds ratio [OR] 2.84, P = 0.008), whereas TTH showed the strongest association with upper back pain (OR 2.74, P = 0.008). Higher WPI and body-pain intensity were associated with higher headache intensity, more monthly headache days, more monthly severe headache days, and higher HIT-6 scores, as well as poorer quality of life and greater depression, anxiety, and insomnia (all P < 0.001). Axial body pain was associated with higher monthly headache days in migraine, whereas upper body pain was associated with higher monthly headache/severe headache days in TTH.

Conclusions: Body pain is more prevalent and widespread in patients with migraine and TTH and is associated with a greater disease burden, potentially reflecting central sensitization. Distinct patterns of regional pain, particularly neck pain in migraine and upper back pain in TTH, may provide clinically relevant insights into underlying nociceptive mechanisms.

Background: Chronic neuropathic pain is frequently accompanied by anxiety and depression, yet the cortical circuit mechanisms underlying this comorbidity remain unclear. The medial orbitofrontal cortex (mOFC) is a key cortical region involved in emotional regulation and valuation, and clinical imaging studies have reported altered mOFC activity in patients with chronic pain. However, it remains unclear how mOFC neuronal activity contributes to both the pain hypersensitivity and anxiodepressive-like behaviors associated with neuropathic pain. This study aimed to determine the pathway-specific roles of mOFC glutamatergic neurons in chronic pain and comorbid affective disturbances.

Methods: Neuropathic pain was induced by chronic constriction injury (CCI) of the sciatic nerve. Pain sensitivity and anxiodepressive-like behaviors were assessed using von Frey, Hargreaves, open field, elevated plus maze, tail suspension, and forced swim tests. Electrophysiological recording and fiber photometry were used to monitor neuronal activity. Neuronal projection tracing identified projection patterns of mOFC glutamatergic neurons to mediodorsal thalamus (MD) and basolateral amygdala (BLA). Chemogenetic and optogenetic manipulations were applied to selectively modulate the mOFC^CaMKIIα-MD and mOFC^CaMKIIα-BLA pathways.

Results: The mOFC glutamatergic neurons are activated in neuropathic pain mice accompanied by anxiodepressive-like phenotypes. Chemogenetic and optogenetic inhibition of mOFC glutamatergic neurons attenuates both pain hypersensitivity and anxiodepressive-like behaviors after nerve injury. Retrograde labeling result revealed two non-overlapping mOFC^CaMKIIα neurons projecting to the MD and BLA, respectively. Selective inhibition of mOFC^CaMKIIα-MD pathway leads to amelioration of CCI-induced pain hypersensitivity. While selective inhibition of mOFC^CaMKIIα-BLA pathway leads to amelioration of CCI-induced anxiodepressive-like behaviors.

Conclusions: The present study has revealed that the critical involvement of mOFC glutamatergic neurons in the comorbidity of chronic pain and affective disturbances. Inhibition of mOFC glutamatergic neurons attenuates both pain hypersensitivity and anxiodepressive-like behaviors after nerve injury. The discrete mOFC^CaMKIIα-MD and mOFC^CaMKIIα-BLA pathway independently control the sensory and affective components of neuropathic pain.

Background: Migraine is a complex sensory processing disorder marked by dysfunctions in both exteroception and interoception. The high frequency of emotional comorbidities suggests significant abnormalities in emotional processing. Persistent interoceptive abnormalities, indicated by widespread homeostatic disturbances, may be a crucial link between migraine and its associated emotional disorders. However, the specific neural mechanism underlying this altered interoception and abnormal emotional function remains under-explored. This study used task-based functional magnetic resonance imaging (fMRI) to investigate the neural mechanisms of interoceptive dysfunction and aberrant emotional processing in migraine and to examine their potential interplay.

Methods: We recruited 29 patients with episodic migraine (EMs) and 31 healthy controls (HCs). Participants underwent fMRI while performing two interoceptive attention tasks (focusing on heartbeat and breathing) and two negative emotion recall tasks (involving pain and anxiety). Statistical analyses included group-level activation mapping, between-group comparisons, generalized psychophysiological interaction (gPPI) for task-modulated functional connectivity, and correlations with clinical characteristics.

Results: Migraine patients exhibited dysfunction within the prefrontal cortex (PFC) during both interoceptive and emotional tasks. During heartbeat attention, patients showed significant hypoactivation in the right superior frontal gyrus (SFG) and reduced functional connectivity between the SFG and frontal pole (FP) compared to controls. This SFG hypoactivation was correlated with greater headache intensity. Conversely, during anxiety recall, patients displayed hyperactivation in the left medial orbitofrontal cortex (mOFC) and enhanced functional connectivity from the mOFC to the SFG. Notably, the degree of mOFC hyperactivation was negatively correlated with depression and anxiety scores.

Conclusions: Our results provide experimental fMRI evidence that migraine involves abnormal interoceptive and emotional processing, with a core dysfunction localized to circuits within the prefrontal cortex. This disrupted PFC activity suggests a fundamental dysregulation in the transformation of bodily signals into conscious awareness. Furthermore, the mOFC-SFG pathway may serve as a key neural substrate mediating the interplay between these interoceptive and emotional abnormalities.

Clinical trial number: Not applicable.