Journal of neurophysiology
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Comparative Study
Activation of spinal d1/d5 receptors induces late-phase LTP of C-fiber-evoked field potentials in rat spinal dorsal horn.
Long-term potentiation (LTP) of C-fiber-evoked field potentials in spinal dorsal horn may be relevant to pathological pain. Our previous work has shown that the late phase of the spinal LTP is protein synthesis-dependent. ⋯ We found the following. 1) Spinal application of SKF 38393, a D1/D5 receptor agonist, induced a slowly developed LTP of C-fiber-evoked field potentials, lasting for >10 h, and the effect was blocked by the D1/D5 antagonist SCH 23390, whereas a D2 receptor agonist (quinpirole) induced depression of C-fiber responses, lasting for 2 h. 2) The potentiation produced by D1/D5 receptor agonist occluded the late phase but not the early phase of the spinal LTP produced by tetanic stimulation. 3) SCH 23390 selectively depressed the late-phase LTP, when applied 40 min before tetanic stimulation. 4) The D1/D5 agonist-induced potentiation is blocked by the protein synthesis inhibitor anisomycin. 5) Activation of protein kinase A by spinal application of 8-Br-cAMP also induced spinal LTP, and the action occluded the potentiation induced by the D1/D5 receptor agonist. These results suggest that the spinal D1/D5 receptors participate in the protein synthesis-dependent late-phase LTP of C-fiber-evoked field potentials in spinal dorsal horn through the cAMP signaling pathway.
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Comparative Study
Application of nucleus pulposus to L5 dorsal root ganglion in rats enhances nociceptive dorsal horn neuronal windup.
Herniation of the nucleus pulposus (NP) from lumbar intervertebral discs commonly results in radiculopathic pain possibly through a neuroinflammatory response. NP sensitizes dorsal horn neuronal responses, but it is unknown whether this reflects a central or peripheral sensitization. To study central sensitization, we tested if NP enhances windup--the progressive increase in the response of a nociceptive spinal neuron to repeated electrical C-fiber stimulation--a phenomenon that may partly account for temporal summation of pain. ⋯ These results are consistent with NP-induced central sensitization. Mechanical responses were not significantly enhanced after saline or NP treatment. We speculate that inflammatory agents released from (or recruited by) NP affect the dorsal root ganglion (and/or are transported to cord) to enhance primary afferent excitation of nociceptive dorsal horn neurons.
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The purpose of this study was to examine if a delay in rehabilitative motor training after spinal cord injury affects functional motor recovery. We studied a skilled motor task in which rats traversed a raised horizontal ladder and we quantified errors in accurate stepping, i.e., foot slips between rungs. After lesions to the dorsal quadrant of the thoracic (T8) spinal cord that aimed to unilaterally sever the corticospinal and rubrospinal tracts, rats were re-trained to walk across the ladder, either immediately after injury or after a 3-mo delay. ⋯ Animals with large lesions to the corticospinal and rubrospinal tracts (>70%) displayed poor recovery from training (especially for delay-trained animals), suggesting that these two pathways were important in mediating improvements in accurate stepping. In addition, recovery of stepping-like reflexes appeared not to contribute to the recovery of accurate stepping given that the time course of reflex recovery was not related to the time course of recovery of accurate stepping. We conclude that training of a skilled motor task that relies on descending control is more beneficial when initiated immediately after a partial spinal cord injury.
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Comparative Study
Calcium-stimulated adenylyl cyclases required for long-term potentiation in the anterior cingulate cortex.
Activity-dependent long-term potentiation (LTP) in the CNS is thought to be important in learning, memory, development, and persistent pain. Here, we report that NMDA receptor-dependent LTP is the major form of long-term plasticity in the anterior cingulate cortex (ACC). ⋯ Activation of calcium-stimulated adenylyl cyclase subtype 1 (AC1) is essential for the induction of LTP in ACC neurons, while AC8 subunit partially contributes to forskolin-induced potentiation. Our results suggest that calcium-stimulated cAMP-dependent signaling pathways play a critical role in cingulate LTP.
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Comparative Study
Can receptor potentials be detected with threshold tracking in rat cutaneous nociceptive terminals?
Threshold tracking of individual polymodal C- and Adelta-fiber terminals was used to assess membrane potential changes induced by de- or hyperpolarizing stimuli in the isolated rat skin-nerve preparation. Constant current pulses were delivered (1 Hz) through a tungsten microelectrode inserted in the receptive field, and the current amplitude was controlled by feedback with a laboratory computer programmed to serially determine the electrical threshold using the method of limits. During threshold tracking, the receptive fields of the fibers were heated (32-46 degrees C in 210 s) or superfused with modified synthetic interstitial fluid containing either 0, 20, 40, 50, or 60 mM [K+], phosphate buffer to pH 5.2 or 6.1, or bradykinin (BK, 10(-8)-10(-5) M). ⋯ Additionally, for these units, activation was preceded by a significant decrease in threshold compared with the tracked thresholds of fibers unresponsive to heat. Bradykinin also led to a significant threshold decrease before activation. In conclusion, the technique of threshold tracking proved suitable to assess changes in excitability resulting from receptor currents evoked by noxious heat and bradykinin in the terminal arborization of cutaneous nociceptors.