Epidural injection of 2-4mg morphine for 7-14 days were given to 18 patients with severe chronic pain. All cases except 2 arachnoiditis had considerable amelioration of pain, which commenced within 2-3min, reached a peak in 10-20min, and was effective for 6-72 hours. Using sensory evoked potentials(SEP) examination for pre-and post-morphine epidural infusion in 18 pain patients, we found the morphine inhibited the action of spinal pain receptor system. It is suggested that morphine reached the subarachnoid space and produced its effect by direct action on the specific opiate receptors in the substantia gelatinosa of the posterior horn cell of the spinal cord.
Arachnoid ; Arachnoiditis ; Chronic Pain* ; Humans ; Injections, Epidural ; Morphine* ; Nociceptors ; Posterior Horn Cells ; Receptors, Opioid ; Spinal Cord ; Subarachnoid Space ; Substantia Gelatinosa

Caudal narcotic analgesia was assessed after the injection of 3mg morphine diluted in 30ml(physiologic) saline into the sacral canal in 15 patients after upper abdominal surgery, in 20 patients after lower abdominal surgery under general anesthesia, and in 20 patients after perianal surgery under caudal block. Pain relief was evaluated by the subsequent need for systemic analgesics. All cases had considerable relief from pain and the morphine was effective for 12 or more hours. There were no significant differences between pain relief of the upper abdominal and lower abdominal surgery group, upper abdomianl and perianal surgery group, and lower abdominal and perianal surgery group (p>0.05, p>0.05, p>0.05). It is suggested that the morphine, which was administered into the sacral, cannal, reached the subarachnoid space and produced it's effect by direct action on the specific opiate receptors in the substantia gelatinosa of the posterior horn cell of the spinal cord. Consequently, whether analgesia from epidural narcotics appears to be segmental in distribution or not is still in controveray.
Analgesia ; Analgesics ; Anesthesia, General ; Humans ; Morphine* ; Narcotics ; Pain, Postoperative* ; Posterior Horn Cells ; Receptors, Opioid ; Spinal Cord ; Subarachnoid Space ; Substantia Gelatinosa

Herpes zoster is characterized by multiple grouped erythematous vesicular eruption on the skin with severe pain. Therefore diagnasis of herpes zoster is clinically easy but effective control of its severe pain is not clear yet. Recently, Behar suggested that morphine which was injected into the epidural space reached subarachnoid space and produced potent analgesic effect by direct action on the specific opiate receptors in the substantia gelatinosa of the posterior horn cell of the spinal cord. On the basis suggestion, we have attempted to treat the severe pain of herpes zoster which was developed on right shoulder, right upper anterior and posterior chest, and posterior auricular area. At the initial block, we inserted the catheter into the 6th cervical intervertebral space and the tip of the catheter was placed in epidural space to 3cm cephalad. Then 3mg of morphine mixed with 10ml of normal saline was adminietered and also right stellate ganglion block with 0. 25% bupivacaine 7ml was combined, therefore effective pain relief was obtained for 11 hours. At second block, additional dose of 2mg of morphine mixed with 10ml of normal saline was administered through the inserted epidural catheter at the initial block without stellate ganglion block, and effective pain relief was obtained for 15 hours. After then, whenever the pain was developed, additional dose of 2mg of morphine was administered as the same procedure of the second block, and the duration of pain relief was extended gradually by the each procedure (for 24 hours after third block and for 49 hours after fourth block). At 5 days after initial block, severe pain was completely subsided. Side effects such as postural hypotension, motor weakness and dizziness was not developed except slightly motor weakness after initial block. This result showed that small dose of morphine injection into the epidural space is effective control of severe pain of herpes zoster.
Bupivacaine ; Catheters ; Dizziness ; Epidural Space ; Herpes Zoster* ; Hypotension, Orthostatic ; Morphine* ; Posterior Horn Cells ; Receptors, Opioid ; Shoulder ; Skin ; Spinal Cord ; Stellate Ganglion ; Subarachnoid Space ; Substantia Gelatinosa ; Thorax

Effective treatments for neuropathic pain are lacking due to our limited understanding of the mechanisms. The circRNAs are mainly enriched in the central nervous system. However, their function in various physiological and pathological conditions have yet to be determined. Here, we identified circFhit, an exon-intron circRNA expressed in GABAergic neurons, which reduced the inhibitory synaptic transmission in the spinal dorsal horn to mediate spared nerve injury-induced neuropathic pain. Moreover, we found that circFhit decreased the expression of GAD65 and induced hyperexcitation in NK1R⁺ neurons by promoting the expression of its parental gene Fhit in cis. Mechanistically, circFhit was directly bound to the intronic region of Fhit, and formed a circFhit/HNRNPK complex to promote Pol II phosphorylation and H2B monoubiquitination by recruiting CDK9 and RNF40 to the Fhit intron. In summary, we revealed that the exon-intron circFhit contributes to GABAergic neuron-mediated NK1R⁺ neuronal hyperexcitation and neuropathic pain via regulating Fhit in cis.
Rats ; Animals ; Posterior Horn Cells/pathology* ; Spinal Cord Dorsal Horn/metabolism* ; Neuralgia ; Synaptic Transmission

Reactive oxygen species (ROS) and nitrogen species (RNS) are involved in cellular signaling processes as a cause of oxidative stress. According to recent studies, ROS and RNS are important signaling molecules involved in pain transmission through spinal mechanisms. In this study, a patch clamp recording was used in spinal slices of rats to investigate the action mechanisms of O₂˙⁻ and NO on the excitability of substantia gelatinosa (SG) neuron. The application of xanthine and xanthine oxidase (X/XO) compound, a ROS donor, induced inward currents and increased the frequency of spontaneous excitatory postsynaptic currents (sEPSC) in slice preparation. The application of S-nitroso-N-acetyl-DLpenicillamine (SNAP), a RNS donor, also induced inward currents and increased the frequency of sEPSC. In a single cell preparation, X/XO and SNAP had no effect on the inward currents, revealing the involvement of presynaptic action. X/XO and SNAP induced a membrane depolarization in current clamp conditions which was significantly decreased by the addition of thapsigargin to an external calcium free solution for blocking synaptic transmission. Furthermore, X/XO and SNAP increased the frequency of action potentials evoked by depolarizing current pulses, suggesting the involvement of postsynaptic action. According to these results, it was estblished that elevated ROS and RNS in the spinal cord can sensitize the dorsal horn neurons via pre- and postsynaptic mechanisms. Therefore, ROS and RNS play similar roles in the regulation of the membrane excitability of SG neurons.
Action Potentials ; Animals ; Calcium ; Excitatory Postsynaptic Potentials ; Humans ; Membranes ; Neurons ; Nitric Oxide ; Nitrogen ; Oxidative Stress ; Posterior Horn Cells ; Rats ; Reactive Oxygen Species ; Spinal Cord ; Substantia Gelatinosa ; Superoxides ; Synaptic Transmission ; Thapsigargin ; Tissue Donors ; Xanthine ; Xanthine Oxidase

OBJECTIVETo study on mechanisms of acupuncture in relieving visceral pain.

METHODSIn SD rats CRD was used as noxious visceral stimuli. Activities of spinal dorsal horn wide dynamic (WDR) neurons of L1-L13 were recorded by extracellular microelectrode technique. Acupuncture was given at ipsi-lateral and contra-lateral Zusanli (ST 36) of the same segmental innervation of rectum and colon.

RESULTSVisceral noxious afferent could significantly activate spinal dorsal horn convergent neurons, and mechanical stimulation of contra-lateral body surface and hand acupuncture at Zusanli (ST 36) could inhibit this noxious response. When the spinal cord was acutely blocked, the inhibiting CRD effect of needling CRD effect of needling contra-lateral Zusanli (ST 36) completely disappeared.

CONCLUSIONAcupuncture and visceral noxious afferent signals converge and interact each other in spinal level, and acupuncture at acupoint can inhibit the spinal dorsal horn neuron respon se activated by visceral noxious afferent and this action needs the participation of the center above the spinal cord.

Dopamine has been generally known to exert antinociceptive action in behavioral pain test, such as tail flick and hot plate test, but there appears to be a great variance in the reports on the antinociceptive effect of dopamine depending on the dosage and route of drug administration and type of animal preparation. In the present study, the effects of dopamine on the responses of wide dynamic range (WDR) cells to mechanical, thermal and graded electrical stimuli were investigated, and the dopamine-induced changes in WDR cell responses were compared between animals with an intact spinal cord and the spinal animals. Spinal application of dopamine (1.3 & 2.6 mM) produced a dose-dependent inhibiton of WDR cell responses to afferent inputs, the pinch-induced or the C-fiber evoked responses being more strongly depressed than the brush-induced or the A-fiber evoked responses. The dopamine-induced inhibition was more pronounced in the spinal cat than in the cat with intact spinal cord. The responses of WDR cell to thermal stimulation were also strongly inhibited. Dopamine D2 receptor antagonist, sulpiride, but not D1 receptor antagonist, significantly blocked the inhibitory action of dopamine on the C-fiber and thermal responses of dorsal horn cells. These findings suggest that dopamine strongly suppresses the responses of WDR cells to afferent signals mainly through spinal dopamine D2 receptors and that spinal dopaminergic processes are under the tonic inhibitory action of the descending supraspinal pathways.
Animals ; Cats* ; Dopamine ; Posterior Horn Cells* ; Receptors, Dopamine D2 ; Spinal Cord ; Sulpiride

The present study was undertaken to confirm whether melittin, a major constituent of whole bee venom (WBV), had the ability to produce the same nociceptive responses as those induced by WBV. In the behavioral experiment, changes in mechanical threshold, flinching behaviors and paw thickness (edema) were measured after intraplantar (i.pl.) injection of WBV (0.1 mg & 0.3 mg/paw) and melittin (0.05 mg & 0.15 mg/paw), and intrathecal (i.t.) injection of melittin (6microgram). Also studied were the effects of i.p. (2 mg & 4 mg/kg), i.t. (0.2microgram & 0.4microgram) or i.pl. (0.3 mg) administration of morphine on melittin- induced pain responses. I.pl. injection of melittin at half the dosage of WBV strongly reduced mechanical threshold, and increased flinchings and paw thickness to a similar extent as those induced by WBV. Melittin- and WBV-induced flinchings and changes in mechanical threshold were dose- dependent and had a rapid onset. Paw thickness increased maximally about 1 hr after melittin and WBV treatment. Time-courses of nociceptive responses induced by melittin and WBV were very similar. Melittin-induced decreases in mechanical threshold and flinchings were suppressed by i.p., i.t. or i.pl. injection of morphine. I.t. administration of melittin (6microgram) reduced mechanical threshold of peripheral receptive field and induced flinching behaviors, but did not cause any increase in paw thickness. In the electrophysiological study, i.pl. injection of melittin increased discharge rates of dorsal horn neurons only with C fiber inputs from the peripheral receptive field, which were almost completely blocked by topical application of lidocaine to the sciatic nerve. These findings suggest that pain behaviors induced by WBV are mediated by melittin-induced activation of C afferent fiber, that the melittin- induced pain model is a very useful model for the study of pain, and that melittin-induced nociceptive responses are sensitive to the widely used analgesics, morphine.
Analgesics ; Bee Venoms* ; Bees* ; Lidocaine ; Melitten* ; Morphine ; Nerve Fibers, Unmyelinated ; Nociception ; Posterior Horn Cells ; Sciatic Nerve

Spinal cord injury often leads to central neuropathic pain syndromes, such as allodynic and hyperalgesic behaviors. Electrophysiologically, spinal dorsal horn neurons show enhanced activity to non-noxious and noxious stimuli as well as increased spontaneous activity following spinal cord injury, which often called hyperexcitability or central sensitization. Under hyperexcitable states, spinal neurons lose their ability of discrimination and encoding somatosensory information followed by abnormal somatosensory recognition to non-noxious and noxious stimuli. In the present review, we summarize a variety of pathophysiological mechanisms of neuronal hyperexcitability for treating or preventing central neuropathic pain syndrome following spinal cord injury.
Animals ; Central Nervous System Sensitization ; Discrimination (Psychology) ; Neuralgia ; Neurons ; Posterior Horn Cells ; Rats ; Spinal Cord ; Spinal Cord Injuries

Long-term potentiation (LTP) of C-fiber evoked field potentials in spinal dorsal horn is first reported in 1995. Since then, the mechanisms underlying the long-lasting enhancement in synaptic transmission between primary afferent C-fibers and neurons in spinal dorsal horn have been investigated by different laboratories. In this article, the related data were summarized and discussed.
Animals ; Evoked Potentials ; Long-Term Potentiation ; Nerve Fibers, Unmyelinated ; physiology ; Posterior Horn Cells ; cytology ; Rats, Sprague-Dawley ; Synaptic Transmission