Pain
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The rostral ventromedial medulla (RVM) exerts both inhibitory and excitatory controls over nociceptive neurons in the spinal cord and medullary dorsal horn. Selective ablation of mu-opioid receptor (MOR)-expressing neurons in the RVM using saporin conjugated to the MOR agonist dermorphin-saporin (derm-sap) attenuates stress and injury-induced behavioral hypersensitivity, yet the effect of RVM derm-sap on the functional integrity of the descending inhibitory system and the properties of RVM neurons remain unknown. Three classes of RVM neurons (on-cells, off-cells, and neutral cells) have been described with distinct responses to noxious stimuli and MOR agonists. ⋯ Furthermore, electrical stimulation of the periaqueductal gray produced analgesia in both derm-sap and saporin controls with similar thresholds. Microinjection of kynurenic acid, a glutamate receptor antagonist, into the RVM disrupted periaqueductal gray stimulation-produced analgesia in both saporin-treated and derm-sap-treated rats. These results indicate that MOR-expressing neurons in the RVM are not required for analgesia produced by either direct or indirect activation of neurons in the RVM.
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Approximately 20% of patients suffering from stroke with pure or predominant sensory symptoms (referred to as sensory stroke patients) develop central poststroke pain (CPSP). It is largely unknown what distinguishes these patients from those who remain pain free. Using quantitative sensory testing (QST), we analyzed the somatosensory profiles of 50 patients with chronic sensory stroke, of which 25 suffered from CPSP. ⋯ In summary, our analysis reveals that CPSP is associated with impaired temperature perception and positive sensory signs, but differences between patients with CPSP and NPSS are subtle. Both patients with CPSP and NPSS show considerable QST changes on the ipsilesional body side. These results are in part paralleled by recent findings of bilaterally spread cortical atrophy in CPSP and might reflect chronic maladaptive cortical plasticity, particularly in patients with CPSP.
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Obesity is associated with several pain disorders including headache. The effects of obesity on the trigeminal nociceptive system, which mediates headache, remain unknown. We used 2 complementary mouse models of obesity (high-fat diet and leptin deficiency) to examine this. ⋯ We observed higher calcium influx in cultured trigeminal ganglia neurons from obese mice and a higher percentage of medium to large diameter capsaicin-responsive cells. These findings demonstrate that obesity results in functional changes in the trigeminal system that may contribute to abnormal sensory processing. Our findings provide the foundation for in-depth studies to improve the understanding of the effects of obesity on the trigeminal system and may have implications for the pathophysiology of headache disorders.
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Pain-related adaptations in movement require a network architecture that allows for integration across pain and motor circuits. Previous studies addressing this issue have focused on cortical areas such as the midcingulate cortex. Here, we focus on pain and motor processing in the human cerebellum. ⋯ Activation in these multimodal regions persisted when pain and motor processes were combined within the same trial, and activation in contralateral left lobule VIIb persisted when stimulation was controlled for. Functional connectivity analyses revealed significant correlations in the BOLD time series between multimodal cerebellar regions and sensorimotor regions in the cerebrum including anterior midcingulate cortex, supplementary motor area, and thalamus. The current findings are the first to show multimodal processing in lobules VI and VIIb for motor control and pain processing and suggest that the posterior cerebellum may be important in understanding pain-related adaptations in motor control.