The action of opioid on the hyperpolarization-activated cation current (Ih) in substantia gelatinosa neurons were investigated by using whole-cell voltage-clamp recording in rat spinal brain slices. Hyperpolarizing voltage steps revealed slowly activating currents in a subgroup of neurons. The half-maximal activation and the reversal potential of the current were compatible to neuronal Ih. DAMGO (1 muM), a selective-opioid agonist, reduced the amplitude of Ih reversibly. This reduction was dose-dependent and was blocked by CTOP (2 muM), a selective mu-opioid antagonist. DAMGO shifted the voltage dependence of activation to more hyperpolarized potential. Cesium (1 mM) or ZD 7288 (100 muM) blocked Ih and the currents inhibited by cesium, ZD 7288 and DAMGO shared a similar time and voltage dependence. These results suggest that activation of mu-opioid receptor by DAMGO can inhibit Ih in a subgroup of rat substantia gelatinosa neurons.
Animals ; Brain ; Cesium ; Enkephalin, Ala(2)-MePhe(4)-Gly(5)- ; Neurons* ; Rats* ; Substantia Gelatinosa*

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

The KA1 kainate receptor (KAR) subunit in the substantia gelatinosa (SG) of the trigeminal subnucleus caudalis (Vc) has been implicated in the processing of nociceptive information from the orofacial region. This study compared the expression of the KA1 KAR subunit in the SG of the Vc in juvenile, prepubescent and adult mice. RT-PCR, Western blot and immunohistochemistry analyses were used to examine the expression level in SG area. The expression levels of the KA1 KAR subunit mRNA and protein were higher in juvenile mice than in prepubescent or adult mice. Quantitative data revealed that the KA1 KAR subunit mRNA and protein were expressed at levels approximately two and three times higher, respectively, in juvenile mice than in adult mice. A similar expression pattern of the KA1 KAR subunit was observed in an immunohistochemical study that showed higher expression in the juvenile (59%) than those of adult (35%) mice. These results show that the KA1 KAR subunits are expressed in the SG of the Vc in mice and that the expression level of the KA1 KAR subunit decreases gradually with postnatal development. These findings suggest that age-dependent KA1 KAR subunit expression can be a potential mechanism of age-dependent pain perception.
Age Factors ; Animals ; Gene Expression Profiling ; *Gene Expression Regulation, Developmental ; Mice ; Receptors, Kainic Acid/*metabolism ; Substantia Gelatinosa/*metabolism

Epidural injection of 2.0 mg morphine with distilled water or 0.9 % normal saline 10 ml were given to a bladder cancer patient with severe chronic intraetable pain which radiated from low abdomen to gluteal and low leg region. The patient had absolute pain relief which began 2~3 minutes to onset, with 3~5 minutes of peak of action and was effective for 20~25 hours (mean 24 hours) without complications or continuous care as an ambulatory patient. It is suggested that the morphine reached the subarachinoid space through the membrane and produced its effect by direct action on the specific opiate receptors in the substantia gelatinosa of the posterior horn of the spinal cord.
Abdomen ; Animals ; Horns ; Humans ; Injections, Epidural ; Leg ; Membranes ; Morphine* ; Receptors, Opioid ; Spinal Cord ; Substantia Gelatinosa ; Urinary Bladder Neoplasms ; Water

OBJECTIVETo investigate the effect of minocycline on hyperpolarization-activated current (Ih) in the substantia gelatinosa (SG) neurons in rat spinal dorsal horn.

METHODSIn vitro spinal cord transverse slices were prepared from 3-5-week-old male Sprague-Dawley rats. Using whole-cell patch clamp technique, Ih currents were recorded before and after bath application of minocycline (1-300 µmol/L) to the SG neurons.

RESULTSIh currents were observed in nearly 50% of the recorded neurons, and were blocked by Ih blocker CsCl and ZD7288. Minocycline rapidly and reversibly reduced the amplitude of Ih and decreased the current density in a concentration-dependent manner with an IC50 of 34 µmol/L.

CONCLUSIONMinocycline suppresses the excitability of SG neurons through inhibiting the amplitude and current density of Ih and thereby contributes to pain modulation.

Animals ; Male ; Minocycline ; pharmacology ; Neurons ; drug effects ; Patch-Clamp Techniques ; Rats ; Rats, Sprague-Dawley ; Substantia Gelatinosa ; cytology

The lamina II, also called the substantia gelatinosa (SG), of the trigeminal subnucleus caudalis (Vc), is thought to play an essential role in the control of orofacial nociception. Glycine and serotonin (5-hydroxytryptamine, 5-HT) are the important neurotransmitters that have the individual parts on the modulation of nociceptive transmission. However, the electrophysiological effects of 5-HT on the glycine receptors on SG neurons of the Vc have not been well studied yet. For this reason, we applied the whole-cell patch clamp technique to explore the interaction of intracellular signal transduction between 5-HT and the glycine receptors on SG neurons of the Vc in mice. In nine of 13 neurons tested (69.2%), pretreatment with 5-HT potentiated glycine-induced current (I(Gly)). Firstly, we examined with a 5-HT₁ receptor agonist (8-OH-DPAT, 5-HT(1/7) agonist, co-applied with SB-269970, 5-HT₇ antagonist) and antagonist (WAY-100635), but 5-HT₁ receptor agonist did not increase IGly and in the presence of 5-HT₁ antagonist, the potentiation of 5-HT on I(Gly) still happened. However, an agonist (α-methyl-5-HT) and antagonist (ketanserin) of the 5-HT₂ receptor mimicked and inhibited the enhancing effect of 5-HT on I(Gly) in the SG neurons, respectively. We also verified the role of the 5-HT₇ receptor by using a 5-HT₇ antagonist (SB-269970) but it also did not block the enhancement of 5-HT on I(Gly). Our study demonstrated that 5-HT facilitated I(Gly) in the SG neurons of the Vc through the 5-HT₂ receptor. The interaction between 5-HT and glycine appears to have a significant role in modulating the transmission of the nociceptive pathway.
Animals ; Glycine ; Mice ; Neurons ; Neurotransmitter Agents ; Nociception ; Patch-Clamp Techniques ; Receptors, Glycine ; Serotonin ; Signal Transduction ; 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

Reactive oxygen species (ROS) and nitrogen species (RNS) are implicated in cellular signaling processes and as a cause of oxidative stress. Recent studies indicate that ROS and RNS are important signaling molecules involved in nociceptive transmission. Xanthine oxidase (XO) system is a well-known system for superoxide anions (O2(.-)) generation, and sodium nitroprusside (SNP) is a representative nitric oxide (NO) donor. Patch clamp recording in spinal slices was used to investigate the role of O2(.-) and NO on substantia gelatinosa (SG) neuronal excitability. Application of xanthine and xanthine oxidase (X/XO) compound induced membrane depolarization. Low concentration SNP (10 microM) induced depolarization of the membrane, whereas high concentration SNP (1 mM) evoked membrane hyperpolarization. These responses were significantly decreased by pretreatment with phenyl N-tert-butylnitrone (PBN; nonspecific ROS and RNS scavenger). Addition of thapsigargin to an external calcium free solution for blocking synaptic transmission, led to significantly decreased X/XO-induced responses. Additionally, X/XO and SNP-induced responses were unchanged in the presence of intracellular applied PBN, indicative of the involvement of presynaptic action. Inclusion of GDP-beta-S or suramin (G protein inhibitors) in the patch pipette decreased SNP-induced responses, whereas it failed to decrease X/XO-induced responses. Pretreatment with n-ethylmaleimide (NEM; thiol-alkylating agent) decreased the effects of SNP, suggesting that these responses were mediated by direct oxidation of channel protein, whereas X/XO-induced responses were unchanged. These data suggested that ROS and RNS play distinct roles in the regulation of the membrane excitability of SG neurons related to the pain transmission.
Animals ; Calcium ; Ethylmaleimide ; Humans ; Membranes ; Neurons* ; Nitric Oxide ; Nitrogen* ; Nitroprusside ; Oxidative Stress ; Rats* ; Reactive Oxygen Species* ; Substantia Gelatinosa* ; Superoxides ; Suramin ; Synaptic Transmission ; Thapsigargin ; Tissue Donors ; Xanthine ; Xanthine Oxidase

In an attempt to find out the effect of epidural administration with morphine on postoperative pain relief, a small dose of morphine with a local anesthetic(lidocaine) was administered into the epidural space, either by lumbar or caudal approach. Morphine injected into the epidural space has been suggested to produce it's effect by direct action on the specific oplate receptor in the substantia gelatinosa of the posterior horn of the spinal cord. 90 patients who were anesthetized under epidural block in the Pusan Paik's Hospital, INJE Medical College, from May 1980 trhough Jan. 1981 were divided into the groups "Lidocaine alone" and "Lidocaine + Morphine". The number of patients of patients of the lumbar approach was 73 (81.1%) and of the caudal approach was 17(18.9%). The group "Lidocaine alone" numbered 45 cases which were injected with 2% lidocaine into the epidural space as an anesthetic. Group "Lidocaine + Morphine" also numbered 45 cases and received 2mg of morphine with 500 mg of 2% lidocaine as an epidural anesthetic. 0.2mg of 0.1% epinephrine was mixed to the anesthetic solution in all the above cases. The results of this study are as follows: 1) Alteration of arterial blood pressure during anesthesia was minimal within 30 minutes after injection of the epidural anesthetic in both groups. 2) Duration of postoperative pain relief in the group "Lidocaine + Morphine" was significantly extended comparing it to that in the group "Lidocaine alone". 3) Between the two groups, no significant difference was noted in recovery of spontaneous volding. 4) Complications were similar in both groups except for nausea and vomiting which occurred more frequently in the group "Lidocaine + Morphine"(8.9% and 6.7%, respectively) than in the group "Lidocaine alone" (2.2% and none, respectively). Any signs of CNS depression or neurologic sequelae were not observed.
Anesthesia ; Anesthesia, Epidural* ; Animals ; Arterial Pressure ; Busan ; Depression ; Epidural Space ; Epinephrine ; Horns ; Humans ; Lidocaine ; Morphine* ; Nausea ; Pain, Postoperative* ; Spinal Cord ; Substantia Gelatinosa ; Vomiting