Disentangling self from pain: mindfulness meditation-induced pain relief is driven by thalamic-default mode network decoupling.

ABSTRACT: For millenniums, mindfulness was believed to diminish pain by reducing the influence of self-appraisals of noxious sensations. Today, mindfulness meditation is a highly popular and effective pain therapy that is believed to engage multiple, nonplacebo-related mechanisms to attenuate pain. Recent evidence suggests that mindfulness meditation-induced pain relief is associated with the engagement of unique cortico-thalamo-cortical nociceptive filtering mechanisms. However, the functional neural connections supporting mindfulness meditation-based analgesia remain unknown. This mechanistically focused clinical trial combined functional magnetic resonance imaging with psychophysical pain testing (49°C stimulation and pain visual analogue scales) to identify the neural connectivity supporting the direct modulation of pain-related behavioral and neural responses by mindfulness meditation. We hypothesized that mindfulness meditation-based pain relief would be reflected by greater decoupling between brain mechanisms supporting appraisal (prefrontal) and nociceptive processing (thalamus). After baseline pain testing, 40 participants were randomized to a well-validated, 4-session mindfulness meditation or book-listening regimen. Functional magnetic resonance imaging and noxious heat (49°C; right calf) were combined during meditation to test study hypotheses. Mindfulness meditation significantly reduced behavioral and neural pain responses when compared to the controls. Preregistered (NCT03414138) whole-brain analyses revealed that mindfulness meditation-induced analgesia was moderated by greater thalamus-precuneus decoupling and ventromedial prefrontal deactivation, respectively, signifying a pain modulatory role across functionally distinct neural mechanisms supporting self-referential processing. Two separate preregistered seed-to-seed analyses found that mindfulness meditation-based pain relief was also associated with weaker contralateral thalamic connectivity with the prefrontal and primary somatosensory cortex, respectively. Thus, we propose that mindfulness meditation is associated with a novel self-referential nociceptive gating mechanism to reduce pain.

The Sphenoparietal Sinus Revisited: Anatomical and Histological Study With Application to Interventional Procedures and Skull Base Surgery.

Background The sphenoparietal sinus (SPS) is implicated in various clinical pathologies, specifically arteriovenous fistulas and venous sinus thrombosis. This study is aimed to better understand this venous structure of the skull base via histological examination. Methods Ten embalmed and latex-injected adult body donors' heads (20 sides) underwent microdissection of the SPS using a surgical microscope. The entire dura on the underside of the lesser wing of the sphenoid bone encompassing the region known as the groove for the SPS was harvested from each body donor and submitted for histological analysis (H&E, Periodic acid-Schiff [PAS], Masson's Trichrome). Five left and five right transverse sinuses were harvested and analyzed histologically as controls. Results A definitive SPS was identified in 14/20 (70%) of the latex-injected body donors. When present, the sinuses were classified as small, medium, or large. Tributaries included the middle meningeal veins, superficial Sylvian vein, and anterior temporal veins. All sinuses drained medially into the cavernous sinus. For the body donors analyzed histologically, 17 (85%) were consistent with a dural venous sinus and not a vein and were observed to have a rich nerve and arterial supply within their walls. The histological findings of the SPS were similar to those seen for the transverse sinus. The combined prevalence for the SPS in gross and histological body donors was 78%. Conclusions Our findings support the presence of SPS in the majority of body donors. To our knowledge, this is the first histological study of the SPS.

Attention to breath sensations does not engage endogenous opioids to reduce pain.

The endogenous opioidergic system is critically involved in the cognitive modulation of pain. Slow-breathing-based techniques are widely used nonpharmacological approaches to reduce pain. Yet, the active mechanisms of actions supporting these practices are poorly characterized. Growing evidence suggest that mindfulness-meditation, a slow-breathing technique practiced by nonreactively attending to breathing sensations, engages multiple unique neural mechanisms that bypass opioidergically mediated descending pathways to reduce pain. However, it is unknown whether endogenous opioids contribute to pain reductions produced by slow breathing. The present double-blind, placebo-controlled crossover study examined behavioral pain responses during mindfulness-meditation (n = 19), sham-mindfulness meditation (n = 20), and slow-paced breathing (n = 20) in response to noxious heat (49°C) and intravenous administration (0.15 mg/kg bolus + 0.1 mg/kg/hour maintenance infusion) of the opioid antagonist, naloxone, and placebo saline. Mindfulness significantly reduced pain unpleasantness ratings across both infusion sessions when compared to rest, but not pain intensity. Slow-paced breathing significantly reduced pain intensity and unpleasantness ratings during naloxone but not saline infusion. Pain reductions produced by mindfulness-meditation and slow-paced breathing were insensitive to naloxone when compared to saline administration. By contrast, sham-mindfulness meditation produced pain unpleasantness reductions during saline infusion but this effect was reversed by opioidergic antagonism. Sham-mindfulness did not lower pain intensity ratings. Self-reported "focusing on the breath" was identified as the operational feature particularly unique to the mindfulness-meditation and slow paced-breathing, but not sham-mindfulness meditation. Across all individuals, attending to the breath was associated with naloxone insensitive pain-relief. These findings provide evidence that slow breathing combined with attention to breath reduces pain independent of endogenous opioids.