The Journal of neuroscience : the official journal of the Society for Neuroscience
-
Mechanisms of inflammatory pain are not fully understood. We investigated the role of TRPV1 (transient receptor potential subtype V1) and TNF-α, two critical mediators for inflammatory pain, in regulating spinal cord synaptic transmission. We found in mice lacking Trpv1 the frequency but not the amplitude of spontaneous EPSCs (sEPSCs) in lamina II neurons of spinal cord slices is reduced. ⋯ Spinal injection of NPD1, at very low doses (0.1-10 ng), blocks spinal LTP and reduces TRPV1-dependent inflammatory pain, without affecting baseline pain. NPD1 also reduces TRPV1-independent but TNF-α-dependent pain hypersensitivity. Our findings demonstrate a novel role of NPD1 in regulating TRPV1/TNF-α-mediated spinal synaptic plasticity and identify NPD1 as a novel analgesic for treating inflammatory pain.
-
Painful events in our environment are often accompanied by stimuli from other sensory modalities. These stimuli may influence the perception and processing of acute pain, in particular when they comprise emotional cues, like facial expressions of people surrounding us. In this whole-head magnetoencephalography (MEG) study, we examined the neuronal mechanisms underlying the influence of emotional (fearful, angry, or happy) compared to neutral facial expressions on the processing of pain in humans. ⋯ The presentation of faces with emotional expressions compared to faces with neutral expressions led to a stronger bilateral suppression of the pain-induced BBA, possibly reflecting enhanced response readiness of the sensorimotor system. Moreover, pain-induced GBA in the sensorimotor cortex was larger for faces expressing fear than for faces expressing anger, which might reflect the facilitation of avoidance-motivated behavior triggered by the concurrent presentation of faces with fearful expressions and painful stimuli. Thus, the presence of emotional cues, like facial expressions from people surrounding us, while receiving acute pain may facilitate neuronal processes involved in the preparation and execution of adequate protective motor responses.
-
Recent evidence indicates the existence of pyramidal cells (PCs) and interneurons with nontrivial tuning characteristics for sound attributes in the primary auditory cortex (A1) of mammals. These neurons are functionally distributed into layers and sparsely organized at a small scale. However, their topological locations at a large scale in A1 have not yet been investigated. ⋯ Spiking activity in these neurons during stimulation was correlated to β (12-25 Hz) and low γ (25-70 Hz) postsynaptic oscillations in the infragranular layer, whereas in the supragranular layer, better correlations were found with high γ (70-170 Hz) oscillations. The time-frequency analysis of the postsynaptic potentials showed a transient broadband power increase in all layers after the stimulus onset that was followed by a sustained high γ oscillation in the supragranular layer, fluctuations in the laminar content of the low-frequency oscillations, and a global attenuation in the low-frequency powers after the stimulus offset that happened together with a long-lasting strengthening of the β oscillations. We concluded that, for rats, sounds are codified in A1 by segregated networks of specialized PCs whose postsynaptic activity impinges on the emergence of sparse/dense spiking patterns.
-
Orexin A and B are hypothalamic peptides known to modulate arousal, feeding, and reward via OX1 and OX2 receptors. Orexins are also antinociceptive in the brain, but their mechanism(s) of action remain unclear. Here, we investigated the antinociceptive mechanism of orexin A in the rat ventrolateral periaqueductal gray (vlPAG), a midbrain region crucial for initiating descending pain inhibition. ⋯ Orexin A produced an overall excitatory effect on evoked postsynaptic potentials and hence increased vlPAG neuronal activity. Intra-vlPAG microinjection of orexin A reduced hot-plate nociceptive responses in rats in a manner blocked by SB 334867 and AM 251. Therefore, orexin A may produce antinociception by activating postsynaptic OX1 receptors, stimulating synthesis of 2-AG, an endocannabinoid, through a Gq-protein-mediated PLC-DAGLα enzymatic cascade culminating in retrograde inhibition of GABA release (disinhibition) in the vlPAG.
-
Comparative Study
Cortical projections of functionally identified thalamic trigeminovascular neurons: implications for migraine headache and its associated symptoms.
This study identifies massive axonal arbors of trigeminovascular (dura-sensitive) thalamic neurons in multiple cortical areas and proposes a novel framework for conceptualizing migraine headache and its associated symptoms. Individual dura-sensitive neurons identified and characterized electrophysiologically in first-order and higher-order relay thalamic nuclei were juxtacellularly filled with an anterograde tracer that labeled their cell bodies and processes. First-order neurons located in the ventral posteromedial nucleus projected mainly to trigeminal areas of primary (S1) as well as secondary (S2) somatosensory and insular cortices. ⋯ Such parallel network of thalamocortical projections may play different roles in the transmission of nociceptive signals from the meninges to the cortex. The findings that individual dura-sensitive Po, LP, and LD neurons project to many functionally distinct and anatomically remote cortical areas extend current thinking on projection patterns of high-order thalamic neurons and position them to relay nociceptive information directly rather than indirectly from one cortical area to another. Such extensive input to diverse cortical areas that are involved in regulation of affect, motor function, visual and auditory perception, spatial orientation, memory retrieval, and olfaction may explain some of the common disturbances in neurological functions during migraine.