Discharge Of Dorsal Horn Neurons Research Articles

Comparison of Postoperative Analgesia Following Epidural Bupivacaine and Epidural Bupivacaine with Verapamil in Orthopaedic Lower Limb Surgeries

Comparison of Postoperative Analgesia Following Epidural Bupivacaine and Epidural Bupivacaine with Verapamil in Orthopaedic Lower Limb Surgeries

Advanced Continuous-Contact Heat Pulse Design for Efficient Temporal Summation of Second Pain (Windup)

Temporal summation of second pain or windup (WU SP) can be reliably evoked in normal human subjects by repetitive heat pulses to the skin at frequencies of 0.33 Hz or more. This phenomenon is dependent on activation of peripheral C-nociceptors and central N-methyl-D-aspartate receptors, resulting in windup of C-fiber–evoked discharges of dorsal horn neurons. Several investigations of heat pain summation have used Peltier devices for intermittent-contact heat pulses to the skin. This method returns the skin to an adapting temperature between each stimulus and can result in distinct first and second pain sensations. An alternative method of temporal summation consists of continuous-contact heat stimuli by computerized Peltier thermodes that can provide rapid heat pulses. Previously used continuous-contact heat pulse trains, however, seemed to lack characteristics that result in efficient WU SP. The present study sought to obtain psychophysical evidence that reliable WU SP can be elicited with an advanced pulse design by using a computerized heat-foil/Peltier thermode. WU SP was elicited by repetitive thermal stimulation of the hands at frequencies of 0.33 Hz but not 0.25 and 0.17 Hz. WU SP stimuli were either adjusted to resemble the heat transfer characteristics of intermittent-contact stimulus trains, or they remained unadjusted. The estimated transmission velocity of impulses giving rise to second pain and WU SP was characteristic of C fibers. More pronounced second pain and efficient WU SP could be elicited with adjusted than with unadjusted heat pulse trains. Thus, specifically designed continuous-contact heat pulses can be used to elicit distinct second pain and robust WU SP, thereby providing an efficient psychophysical test of this phenomenon. Perspective Temporal summation testing is rapidly becoming a relevant psychophysical tool for the study of chronic pain disorders. The results of this study will allow more efficient use of currently available constant-contact thermodes for clinical and research applications.

Second phase of formalin-induced excitation of spinal dorsal horn neurons in spinalized rats is reversed by sciatic nerve block.

Considerable debate persists concerning peripheral vs. central mechanisms underlying the second phase of the nociceptive response in the formalin test in the rat. To gain insight into the neurophysiological basis of this pain, we investigated the effects of block of afferent nerve conduction during the second phase of formalin-evoked excitation of single nociceptive neurons recorded extracellularly from rat spinal dorsal horn segments (L(3-4)) in pentobarbital-anaesthetized, male Sprague-Dawley rats. Rats were spinally transected (T(9)) to examine exclusively peripheral and spinal nociceptive processing. In six control rats, hind paw intraplantar formalin injection (50 microL, 2.5%) induced the typical biphasic increase in the discharge rate of the six wide dynamic range neurons tested. This response consisted of a relatively brief immediate phase (approximately 5 min), followed by decreased firing. An ensuing second phase of elevated discharge began approximately 35 min after injection and persisted to at least 80 min. In this control group, 0.9% saline was applied to the exposed ipsilateral sciatic nerve after onset of the second phase (40 min after formalin injection). In a group of six test rats, application of 2% lidocaine instead of saline reversed the second phase of excitation in all six wide dynamic range neurons examined. When the firing rate was normalized to that at 40 min (100%), the time of saline or lidocaine administration, the rate at 50 min was 120 +/- 7.5% in the saline-treated group and 31 +/- 7.4% in the lidocaine-treated group; following lidocaine treatment firing rate remained markedly less than that before administration throughout the remainder of the recording. It is concluded that: (i) spinal mechanisms alone are not sufficient for induction and maintenance of second phase increased discharge of spinal nociceptive dorsal horn neurons; (ii) descending influences via supraspinal inputs are not causal in the development and maintenance of second phase increased discharge and (iii) tonic input from afferent neurons during the second phase plays a primary and essential role in generating and sustaining the second phase of elevated discharge of dorsal horn neurons and, thus, presumably the second phase of nociceptive scores in the formalin test. The data in this study reveal how much of an altered synaptically elicited response in the spinal dorsal horn can be attributed to postsynaptic plastic changes vs. how much can be simply due to increased synaptic input. The present results are important not only in the context of the formalin test but also in the context of other models related to inflammatory pain and neuropathic pain.

Stimulation of the MLR inhibits the discharge of dorsal horn neurons responsive to muscular contraction

We found that electrical stimulation of the mesencephalic locomotor region (MLR) inhibited the discharge of deep dorsal horn neurons receiving group III afferent input from the triceps surae muscles. In contrast, contraction of these muscles induced by electrical stimulation of the tibial nerve activated these dorsal horn neurons. Our findings show that descending central motor commands can inhibit dorsal horn interneurons receiving input from group III afferents during exercise.

Fictive locomotion and scratching inhibit dorsal horn neurons receiving thin fiber afferent input.

In decerebrate paralyzed cats, we examined the effects of two central motor commands (fictive locomotion and scratching) on the discharge of dorsal horn neurons receiving input from group III and IV tibial nerve afferents. We recorded the impulse activity of 74 dorsal horn neurons, each of which received group III input from the tibial nerve. Electrical stimulation of the mesencephalic locomotor region (MLR), which evoked fictive static contraction or fictive locomotion, inhibited the discharge of 44 of the 64 dorsal horn neurons tested. The mean depth from the dorsal surface of the spinal cord of the 44 neurons whose discharge was inhibited by MLR stimulation was 1.77 +/- 0.04 mm. Fictive scratching, evoked by topical application of bicuculline to the cervical spinal cord and irritation of the ear, inhibited the discharge of 22 of the 29 dorsal horn neurons tested. Fourteen of the twenty-two neurons whose discharge was inhibited by fictive scratching were found to be inhibited by MLR stimulation as well. The mean depth from the dorsal surface of the cord of the 22 neurons whose discharge was inhibited by fictive scratching was 1.77 +/- 0.06 mm. Stimulation of the MLR or the elicitation of fictive scratching had no effect on the activity of 22 dorsal horn neurons receiving input from group III and IV tibial nerve afferents. The mean depth from the dorsal surface of the cord was 1.17 +/- 0.07 mm, a value that was significantly (P < 0.05) less than that for the neurons whose discharge was inhibited by either MLR stimulation or fictive scratching. We conclude that centrally evoked motor commands can inhibit the discharge of dorsal horn neurons receiving thin fiber input from the periphery.

Cellular mechanisms of hyperalgesia and spontaneous pain in a spinalized rat model of peripheral neuropathy: changes in myelinated afferent inputs implicated.

Various hypotheses have been proposed to account for the mechanical hyperalgesia and spontaneous pain seen in animal models of peripheral neuropathy. The purpose of the present study was to determine whether there exists a spinal neuronal correlate to these properties. An experimental neuropathy was induced in male Sprague-Dawley rats by placing a 2-mm PE-90 polyethylene cuff around the sciatic nerve. All rats were subsequently confirmed to exhibit mechanical allodynia in the von Frey test. After induction of anaesthesia with pentobarbital and acute spinalization at T9, electrophysiological experiments were performed, recording extracellular single unit activity from ipsi- and contralateral wide dynamic range dorsal horn neurons in spinal segments L1-4. On-going activity was greater in short-term (11-22 days after cuff implantation) and long-term (42-52 days) cuff-implanted rats; 38 spikes/s in short-term versus 19 spikes/s in controls; 29 spikes/s in long-term ipsi- and contralateral neurons. Receptive fields in controls were always restricted, but in almost all cuff-implanted rats extended over the whole hind paw. Responses to noxious mechanical (pinch) and noxious heat stimulation of the cutaneous receptive field in controls consisted of the typical fast initial discharge followed by an afterdischarge. In all neurons from cuff-implanted rats the initial discharge resembled that in controls. However, the afterdischarge, particularly that in response to noxious pinch, was markedly greater in both magnitude and duration. It is suggested that the greater on-going discharge is the cellular correlate of spontaneous pain, and the potentiation of the afterdischarge in response to noxious stimulation is the correlate of hyperalgesia. Given that acutely spinalized rats were tested, only peripheral and/or spinal mechanisms can be considered to explain these data. Considering all the data, it can be concluded that there is a greater change in fibres mediating noxious mechanical than noxious thermal inputs. Among different hypotheses, the one with which the present data are most compatible is that which proposes that chronic nerve injury or inflammation induces phenotypic changes predominantly in myelinated afferents. There may be a redistribution of membrane-bound ion channels, predominantly sodium channels, which leads to ectopic activity and thus spontaneous discharge of dorsal horn neurons. With regard to mechanical stimulation-evoked synaptic input, the central terminals of myelinated afferents expand into regions of the spinal cord which normally receive their predominant input from unmyelinated nociceptive afferents. This may be coupled with a change in these myelinated afferents so that they now synthesize and release peptides, primarily substance P, from their central terminals with the result that the effects of their chemical mediators of synaptic transmission add to the effects of nociceptive inputs leading to exaggerated responses to painful stimuli, thus the basis of clinical hyperalgesia.

Antagonism of nociceptive responses of cat spinal dorsal horn neurons in vivo by the NK-1 receptor antagonists CP-96,345 and CP-99,994, but not by CP-96,344.

Extracellular and intracellular studies were undertaken to test the effects of the non-peptide, substance P (NK-1) receptor antagonists CP-96,345 and CP-99,994, and of CP-96,344, the inactive enantiomer of CP-96,345, on the responses of spinal dorsal horn neurons to peripheral noxious and non-noxious cutaneous stimuli in spinalized cats anesthetized with alpha-chloralose. The effect of these agents on the response of dorsal horn neurons to iontophoretic application of substance P was also tested in extracellular studies. The substance P-induced slow, prolonged discharge of dorsal horn neurons was blocked by administration (0.5 mg/kg, i.v.) of CP-96,345 (n = 10) or CP-99,994 (n = 9), but was unaffected by CP-96,344 (n = 9). The response of substance P-sensitive neurons to noxious thermal stimulation of the cutaneous receptive field, especially the late afterdischarge phase, was also significantly inhibited by CP-96,345 (n = 10) and by CP-99,994 (n = 7). The response of such neurons to noxious pinch stimulation of the receptive field was also significantly inhibited by CP-96,345 (n = 7) and CP-99,994 (n = 8), but the response of three other substance P-sensitive neurons to pinch was unaffected by CP-96,345. CP-96,344 did not affect the response of any neuron tested to either of these noxious stimuli (noxious thermal, n = 7; pinch, n = 6). The response to hair afferent stimulation was unaffected by any of these compounds (CP-96,345, n = 16; CP-96,344, n = 5; CP-99,994, n = 6). In intracellular studies, the effect of these antagonists was tested on responses of dorsal horn neurons to noxious pinch stimulation or to a train of high intensity electrical stimulation of the superficial peroneal nerve. Both stimuli produced an initial fast depolarization followed by a slow and prolonged depolarization with corresponding discharge patterns. CP-96,345 (n = 3) and CP-99,994 (n = 6) selectively blocked the late, slow components of the stimulus-evoked response without affecting the early components. Responses to single electrical pulses of the same intensity and duration were not affected. CP-96,344 did not affect any of the responses tested (n = 5). The data indicate that nociceptive responses of a subset of spinal dorsal horn cells are selectively blocked by the NK-1 receptor antagonists, CP-96,345 and CP-99,994, thus confirming the involvement of NK-1 receptors in these responses.(ABSTRACT TRUNCATED AT 400 WORDS)

Inhibition by etorphine of the discharge of dorsal horn neurons: Effects on the neuronal response to both high- and low-threshold sensory input in the decerebrate spinal cat

The effect of etorphine on the receptive field characteristics of neurons sensitive to brush-touch-pinch and brush-touch was examined. It was found that, aside from the depression of the neuronal response to pinch and the depression of the Ad- and C-fiber responses evoked by receptive field stimulation, etorphine at the same doses attenuated the response to brush-touch as well in about 20% of the cells. Close examination of this phenomenon revealed, first, that in these cells there was a small but detectable reduction in the extent of the brush-touch field. Second, it was found that the response to A-fiber volleys produced by stimulating beyond the edge of the natural brush-touch receptive field produced an evoked discharge which was strongly inhibited by etorphine, unlike the A-fiber input, which derived from electrical stimulation in the center of the brush-touch field. The lack of effect on A-fiber input derived from the center of the brush-touch field was not due to stimulus strength, as no effect of etorphine was observed at threshold currents. In any case, the inhibition of either high- or low-thresh-old input was pharmacologically specific, i.e., it was dose dependent, antagonized by naloxone, produced by two opiate agonists (morphine and etorphine), and not produced by dextrophan. These data suggest that, although the most prominent effect on cellular discharge is that related to high-threshold stimulation and small-fiber input, a measurable degree of depression could be detected at low doses of etorphine in cells which were responsive only to innocuous stimuli.