Rapid generation of OPC-like cells from human pluripotent stem cells for treating spinal cord injury

Remyelination via the transplantation of oligodendrocyte precursor cells (OPCs) has been considered as a strategy to improve the locomotor deficits caused by traumatic spinal cord injury (SCI). To date, enormous efforts have been made to derive OPCs from human pluripotent stem cells (hPSCs), and significant progress in the transplantation of such cells in SCI animal models has been reported. The current methods generally require a long period of time (>2 months) to obtain transplantable OPCs, which hampers their clinical utility for patients with SCI. Here we demonstrate a rapid and efficient method to differentiate hPSCs into neural progenitors that retain the features of OPCs (referred to as OPC-like cells). We used cell sorting to select A2B5-positive cells from hPSC-derived neural rosettes and cultured the selected cells in the presence of signaling cues, including sonic hedgehog, PDGF and insulin-like growth factor-1. This method robustly generated neural cells positive for platelet-derived growth factor receptor-α (PDGFRα) and NG2 (~90%) after 4 weeks of differentiation. Behavioral tests revealed that the transplantation of the OPC-like cells into the spinal cords of rats with contusive SCI at the thoracic level significantly improved hindlimb locomotor function. Electrophysiological assessment revealed enhanced neural conduction through the injury site. Histological examination showed increased numbers of axon with myelination at the injury site and graft-derived myelin formation with no evidence of tumor formation. Our method provides a cell source from hPSCs that has the potential to recover motor function following SCI.

Effects of Human Mesenchymal Stem Cell Transplantation Combined with Polymer on Functional Recovery Following Spinal Cord Hemisection in Rats

The spontaneous axon regeneration of damaged neurons is limited after spinal cord injury (SCI). Recently, mesenchymal stem cell (MSC) transplantation was proposed as a potential approach for enhancing nerve regeneration that avoids the ethical issues associated with embryonic stem cell transplantation. As SCI is a complex pathological entity, the treatment of SCI requires a multipronged approach. The purpose of the present study was to investigate the functional recovery and therapeutic potential of human MSCs (hMSCs) and polymer in a spinal cord hemisection injury model. Rats were subjected to hemisection injuries and then divided into three groups. Two groups of rats underwent partial thoracic hemisection injury followed by implantation of either polymer only or polymer with hMSCs. Another hemisection-only group was used as a control. Behavioral, electrophysiological and immunohistochemical studies were performed on all rats. The functional recovery was significantly improved in the polymer with hMSC-transplanted group as compared with control at five weeks after transplantation. The results of electrophysiologic study demonstrated that the latency of somatosensory-evoked potentials (SSEPs) in the polymer with hMSC-transplanted group was significantly shorter than in the hemisection-only control group. In the results of immunohistochemical study, beta-gal-positive cells were observed in the injured and adjacent sites after hMSC transplantation. Surviving hMSCs differentiated into various cell types such as neurons, astrocytes and oligodendrocytes. These data suggest that hMSC transplantation with polymer may play an important role in functional recovery and axonal regeneration after SCI, and may be a potential therapeutic strategy for SCI.

The Role of the Peripheral Chemokine, CCL3, in Hyperalgesia following Peripheral Nerve Injury in the Rat / 대한통증학회지

BACKGROUND: Upregulation of one type of the pro-inflammatory chemokine (CCL2) and its receptor (CCR2) following peripheral nerve injury contributes to the induction of neuropathic pain. Here, we examined whether another type of chemokine (CCL3) is involved in neuropathic pain. METHODS: We measured changes in mechanical and thermal sensitivity in the hind paws of naive rats or rats with an L5 spinal nerve ligation (SNL) after intra-plantar injection of CCL3 or met-RANTES, an antagonist of the CCL3 receptor, CCR1. We also measured CCL3 levels in the sciatic nerve and the hind paw skin as well as CCR1 expression in dorsal root ganglion (DRG) cells from the lumbar spinal segments. RESULTS: Intra-plantar injection of CCL3 into the hind paw of naive rats mimicked L5 SNL-produced hyperalgesia. Intra-plantar injection of met-RANTES into the hind paw of rats with L5 SNL attenuated hyperalgesia. L5 SNL increased CCL3 levels in the sciatic nerve and the hind paw skin on the affected side. The number of CCR1-positive DRG cells in the lumbar segments was not changed following L5 SNL. CONCLUSIONS: Partial peripheral nerve injury increases local CCL3 levels along the degenerating axons during Wallerian degeneration. This CCL3 binds to its receptor, CCR1, located on adjacent uninjured afferents, presumably nociceptors, to induce hyperalgesia in the neuropathic pain state.

Spinal and Peripheral GABA-A and B Receptor Agonists for the Alleviation of Mechanical Hypersensitivity following Compressive Nerve Injury in the Rat / 대한통증학회지

BACKGROUND: This study was conducted to investigate the roles of the spinal and peripheral gamma-aminobutyric acid (GABA)-ergic systems for the mechanical hypersensitivity produced by chronic compression of the dorsal root ganglion (CCD). METHODS: CCD was performed at the left 5th lumbar dorsal root ganglion. The paw withdrawal threshold (PWT) to von Frey stimuli was measured. The mechanical responsiveness of the lumbar dorsal horn neurons was examined. GABAergic drugs were delivered with intrathecal (i.t.) or intraplantar (i.pl.) injection or by topical application onto the spinal cord. RESULTS: CCD produced mechanical hypersensitivity, which was evidenced by the decrease of the PWT, and it lasting for 10 weeks. For the rats showing mechanical hypersensitivity, the mechanical responsiveness of the lumbar dorsal horn neurons was enhanced. A similar increase was observed with the normal lumbar dorsal horn neurons when the GABA-A receptor antagonist bicuculline was topically applied. An i.t. injection of GABA-A or GABA-B receptor agonist, muscimol or baclofen, alleviated the CCD-induced hypersensitivity. Topical application of same drugs attenuated the CCD-induced enhanced mechanical responsiveness of the lumbar dorsal horn neurons. CCD-induced hypersensitivity was also improved by low-dose muscimol applied (i.pl.) into the affected hind paw, whereas no effects could be observed with high-dose muscimol or baclofen. CONCLUSIONS: The results suggest that the neuropathic pain associated with compression of the dorsal root ganglion is caused by hyperexcitability of the dorsal horn neurons due to a loss of spinal GABAergic inhibition. Peripheral application of low-dose GABA-A receptor agonist can be useful to treat this pain.

Role of Peripheral Glutamate Receptors to Mechanical Hyperalgesia following Nerve Injury or Antidromic Stimulation of L5 Spinal Nerve in Rats with the Previous L5 Dorsal Rhizotomy / 대한통증학회지

BACKGROUND: Peripheral nerve injury leads to neuropathic pain, including mechanical hyperalgesia (MH). Nerve discharges produced by an injury to the primary afferents cause the release of glutamate from both central and peripheral terminals. While the role of centrally released glutamate in MH has been well studied, relatively little is known about its peripheral role. This study was carried out to determine if the peripherally conducting nerve impulses and peripheral glutamate receptors contribute to the generation of neuropathic pain. METHODS: Rats that had previously received a left L5 dorsal rhizotomy were subjected to a spinal nerve lesion (SNL) or brief electrical stimulation (ES, 4 Hz pulses for 5 min) of the left L5 spinal nerve. The paw withdrawal threshold (PWT) to von Frey filaments was measured. The effects of an intraplantar (i.pl.) injection of a glutamate receptor (GluR) antagonist or agonist on the changes in the SNL- or ES-produced PWT was investigated. RESULTS: SNL produced MH, as evidenced by decrease in the PWT, which lasted for more than 42 days. ES also produced MH lasting for 7 days. MK-801 (NMDAR antagonist), DL-AP3 (group-I mGluR antagonist), and APDC (group-II mGluR agonist) delayed the onset of MH when an i.pl. injection was given before SNL. The same application blocked the onset of ES-induced MH. NBQX (AMPA receptor antagonist) had no effect on either the SNL- or ES-induced onset of MH. When drugs were given after SNL or ES, MK-801 reversed the MH, whereas NBQX, DL-AP3, and APDC had no effect. CONCLUSIONS: Peripherally conducting impulses play an important role in the generation of neuropathic pain, which is mediated by the peripheral glutamate receptors.

Loss of the Spinal GABAergic System Is Involved in Chronic Central Pain Following a Spinal Cord Injury; Behavioral and Electrophysiological Evidences / 대한마취과학회지

BACKGROUND: Allodynia, hyperalgesia, and spontaneous pain are symptoms characterized by chronic central pain which was frequently observed following a spinal cord injury (SCI). However, the underlying mechanism has not been fully understood. This study was conducted to investigate whether the loss of the GABAergic system in the spinal dorsal horn was involved in the development of central pain following a spinal cord injury. METHODS: SCI was induced by a hemisection of the spinal cord at T13 in adult male Sprague-Dawley rats. Mechanical allodynia was tested by measuring paw withdrawal frequency in response to repeated applications of a von Frey hair to the plantar surface of the hind-paw. Single neuronal activity of the dorsal horn neurons (L4 L6) was recorded extracellularly using a carbon filament-filled glass microelectrode (2 4 MOhm). The drugs were intrathecally or topically administrated on the spinal surface for behavioral and electrophysiological experiments, respectively. RESULTS: After a left spinal hemisection at T13, behavioral signs of mechanical allodynia developed on both hind-paws and responsiveness of spinal dorsal horn neurons increased on both sides of the spinal dorsal horn. GABA receptor agonists including GABAA and GABAB receptor subtypes suppressed mechanical allodynia on both sides of hind-paws and decreased responsiveness of spinal dorsal horn neurons on both sides of spinal cord. CONCLUSIONS: These results indicate that a loss of the GABAergic system within the spinal cord plays a key role on the development of central pain following a spinal cord injury.

Effects of iontophoretically applied substance P, calcitonin gene-related peptide on excitability of dorsal horn neurones in rats

Spontaneous pain, allodynia and hyperalgesia are well known phenomena following peripheral nerve or tissue injury, and it is speculated that secondary hyperalgesia and allodynia, are generally thought to depend on a hyperexcitability (sensitization) of neurons in the dorsal horn. It is supposed that the sensitization may be due to various actions of neurotransmitters (SP, CGRP, excitatory amino acids) released from the primary afferent fibers. In this study, we examined effects of the iontophoretically applied SP and CGRP on the response to EAA receptor agonists (NMDA and non-NMDA) in the WDR dorsal horn neurones and see if the effects of SP or CGRP mimic the characteristic response pattern known in various pain models. The main results are summarized as follows: 1) SP specifically potentiated NMDA response. 2) CGRP non-specifically potentiated both NMDA and AMPA responses. Potentiation of NMDA response, however, was significantly greater than that of AMPA response. 3) 50% of SP applied cells and 15.8% of CGRP applied cells showed reciprocal changes(potentiation of NMDA response and suppression of AMPA response). These results are generally consistent with the sensitization characteristics in diverse pain models and suggests that the modulatory effects of SP and CGRP on NMDA and non-NMDA (AMPA) response are, at least in part, contribute to the development of sensitization in various pain models.

A change of nitric oxide in rat DRG following Freund's Complete Adjuvant induced inflammtory pain / 대한해부학회지

It has been reported that injection of Freund's complete adjuvant (FCA) into the hindpaw of a rat induces inflammatory responses with accompanying pain behaviors. Signs of pain behaviors observed in FCA-injected animals were reported to be similar to symptoms seen in patients with inflammatory pain. The nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) is a selective histochemical marker for the nitric oxide synthesizing enzyme, nitric oxide synthase (NOS). N (G)-nitro-L-arginine methyl ester (L-NAME) is a NOS inhibitor. In the present study, we examined if inflammaory pain causes increases in NADPH-diaphorase reactivities in neurons of the dorsal root ganglia (DRG). The results were as follows; 1. FCA-induced inflammation on a limb increased staining density (SD) of NADPH-d positive neurons in the ipsilateral side DRG. 2. Pretreatment of L-NAME did not changed SD of NADPH-d positive neurons on the inflammation of contralateral side DRG 3. Posttreatment of L-NAME decreased the inflammation induced SD of NADPH-d positive neurons. 4. n-NOS immunoreactivity did not match NADPH-d histochemical study, implying the constant level of enzyme itself. Inflammation pain on a hindlimb increased staining density of NADPH-diaphorase positive neuron in the DRG, which was decreased by L-NAME. L-NAME also decreased pain perception. This suggests a role of NO in the pain perception and/or modulation at the level of DRG.

Dextromethorphan Pretreatment Does not Reduce the Tourniquet Pain in Normal Volunteers / 대한마취과학회지

BACKGROUND: Dextromethorphan (DEX) is an NMDA receptor antagonist which has recently been introduced for the treatment of chronic pain mainly to reduce the central sensitization component of pain. It is also reported to reduce the pain from acute ischemia of an extremity in a rat model which has a similar mechanism as tourniquet pain. The purpose of this experiment was to see if dextromethorphan could reduce tourniquet pain in normal volunteers. METHODS: A double blind randomized cross-over test was done on ten healthy male volunteers. Each subject was orally administered with three different doses of DEX (placebo, 30, 60 mg) 1 h before the study according to a preallocated randomized table. The subject was not reallocated for the test within two weeks of the previous test. After a 10 minute acclimation period before each test, the degree of tourniquet pain measured by VAS, arterial blood pressure, heart rate, respiration rate, and pressure-evoked pain were measured before and every 5 minutes after inflation of the tourniquet until the subject felt unbearable pain. A mixed model for repeated measurement of data was used for statistical analysis (P 0.05). CONCLUSIONS: DEX is not effective in controlling tourniquet pain in normal awake subjects.

Adrenergic sensitivity of uninjured C-fiber nociceptors in neuropathic rats

We investigated the adrenergic sensitivity of afferent fibers in the L4 dorsal roots of rats with a unilateral ligation of the L5-L6 spinal nerves. About 12% of nociceptive fibers on the affected side were excited by sympathetic stimulation or by intra-arterial injection of norepinephrine which did not affect A beta-fiber activity. Sympathetic excitation of nociceptive fibers was suppressed by alpha 1-antagonist prazosin, while it was unaffected by alpha 2-antagonist yohimbine. Most of these fibers were excited by intra-arterial injection of alpha 1-agonist phenylephrine, without being affected by an injection of alpha 2-agonist clonidine. Sympathetic excitation was blocked by lidocaine applied near the receptive fields of recorded fibers. The results suggested that some nociceptors remaining intact after partial nerve injury become sensitive to sympathetic activity by the mediation of alpha 1-adrenoceptors in the peripheral endings.

Effects of Substance P Antagonist, D-Arg, D-Phe, D-Trp, Leu- Substance P on the Mechanical Hyperalgesia of Inflammation Induced by Freund's Complete Adjuvant in Rat Paw / 대한마취과학회지

BACKGROUND: The effect of substance P (SP) on the hyperalgesia induced by inflammation is controversial, and as SP remains in the periphery just for a short period of time after release from the nerve ending, the contribution of SP on the development of sustained mechanical hyperalgesia in rats with inflammation is questionable. The purpose of this experiment is to evaluate the effect of SP on the development of mechanical hyperalgesia induced by Freund's complete adjuvant (FCA) using SP antagonist [D-Arg, D-Phe, D-Trp, Leu]-substance P (SPA). METHODS: Male Sprague Dawley rats were divided into four groups; control (normal saline) and three different doses of SPA (0.25 microgram, 2.5 microgram, 25 microgram/0.1 ml). Inflammation was induced in rats by injecting 0.15 ml of FCA intraplantarly. Rats showed typical hyperalgesia within 12 hours after injection and maintained it for about one week. To test the effect of SPA on the developement of inflammation, either SPA or saline was injected at 1 h before and at the time of FCA injection under light halothane anesthesia after a baseline test. The effect of SPA on hyperalgesia was assessed by measuring mechanical hyperalgesia at 2, 6, 12, 24 hrs and 4 days after injection of the drug. To test the effect of SPA on fully developed inflammation, tests were done 2 days after injection of FCA. Mechanical hyperalgesias were assessed at 15, 30, 60, 90, 120 min after the drug injections. RESULTS: SPA injected to suppress the initial SP spill over decreased the mechanical hyperalgesia in a dose dependent manner. SPA injected after the full development of inflammation also decreased mechanical hyperalgesia. CONCLUSIONS: SP released at the initial phase of inflammation as well as SP released after the development of inflammation are all important for the maintainance of mechanical hyperalgesia.

The Role of Spinal NO on the Mechanical Allodynia in the Inflammation Model by Freund's Complete Adjuvant / 대한마취과학회지

BACKGROUND: The effect of spinal nitric oxide (NO) on mechanical allodynia brought about by Freund's complete adjuvant (FCA)-induced inflammation is not known. From our previous experiment nitric oxide synthase (NOS) inhibitor nitroG-L-arginine methyl ester (L-NAME) given intraplantarly during the induction period decreased a mechanical hyperalgesia occurring because of FCA-induced inflammation. Therefore, we investigated the spinal effect of NO on mechanical allodynia after the development of allodynia produced by FCA-induced inflammation in rats. METHODS: Male Sprague Dawley rats were prepared with lumbar intrathecal catheter implantation. Inflammation was induced in the rats by injecting 0.1 ml of FCA under halothane anesthesia. Behavioral tests were done 1, 3, 6, 24, and 48 hours after injection of FCA. In the other group, intrathecal L-NAME (10 microgram) was given prior to FCA injection to examine the effect of pretreatment. On postinjection day 2, either L-NAME (10 microgram) or methylene blue (10 and 30 microgram) was administered intrathecally after the baseline measurement. The withdrawal response on mechanical allodynia was assessed by applying von Frey filaments to the right lesioned hindpaw and contralateral paw (as control) at 15, 30, 45, 60, 90, and 120 minutes. Sodium nitroprusside was administered intrathecally to determine the reversal effect of increased threshold in the L-NAME group. RESULTS: Injection of FCA produced a significant mechanical allodynia over time. Pretreatment with L-NAME did not prevent such a mechanical allodynia. Intrathecal L-NAME, but not methylene blue, reduced the mechanical allodynia, which was reversed by sodium nitroprusside. CONCLUSIONS: Spinal NO is likely invloved in the mechanism of the development and maintenance of mechanical allodynia in a state of FCA-induced inflammation.

Transcutaneous Electrical Nerve Stimulation and Microcurrent Electrical Neuromuscular Stimulation on Pain Behaviors in Rats with an Experimental Neuropathy

OBJECTIVE: The present study was conducted to investigate the effects of transcutaneous electrical nerve stimulation (TENS) and microcurrent electrical neuromuscular stimulation (MENS) on pain-like behaviors developed in rats with an experimental neuropathy. METHOD: Neuropathic surgery was done by a unilateral ligation of L5 and L6 spinal nerves of the rat. Allodynic behavior was examined by measuring foot withdrawal frequency in response to 10 applications of a von Frey filament (2.5 g) to the plantar surface of the foot. Ongoing pain behavior was examined by measuring cumulative time in 3 min that the rat lifted its foot off a plate held at cold temperature (5oC). TENS (square pulses; 3 Hz, 30 mA) or MENS (bipolar pulses; 10 Hz, 300 microampere) was applied for 15 min or 5 min, respectively, to the skin of the affected foot. RESULTS: Behavioral signs of mechanical allodynia and cold-induced ongoing pain had developed after nerve injury. Either TENS or MENS, when applied once, alleviated allodynic behavior, lasting up to 2 hrs. Such an alleviation lasted much longer when TENS or MENS was applied repeatedly (once a day for 6 days); 3 days by TENS and 1 day by MENS. Cold-induced ongoing pain behavior, however, was not affected by the repeated application of either TENS or MENS. CONCLUSION: The results suggest that both TENS and MENS are useful tools for the treatment of mechanical allodynia. Repeated application of TENS or MENS is more effective in alleviating mechanical allodynia than its single application. Either TENS or MENS, however, seems not effective in alleviating cold-induced ongoing pain.

Enflurane Anesthesia Augments the Peripheral Venous Pressure Changes during Non-invasive Blood Pressure Measurement / 대한마취과학회지

BACKGROUND: Venous regurgitation into the infusion line and subsequent occlusion frequently occurs during blood pressure (BP) measurement. The purpose of this study was to obtain the pattern and the actual range of peripheral venous pressure (PVP) change during NIBP measurement before and during enflurane anesthesia. METHODS: Adult size NIBP cuff was placed on the same arm on which IV infusion set was placed. PVP waveforms during BP measurement were recorded from 6 subjects. PVPs were measured before induction and at 30 min after induction of enflurane anesthesia (n=19). As the PVP waveform during NIBP measurement was biphasic in shape, values of baseline PVP (BEFORE), first peak (PEAK1), notch between two peaks (NOTCH), second peak (PEAK2) were measured. Timed control data were obtained from six volunteers. RESULTS: PEAK2 was always higher than PEAK1. Range of peak PVP was 12-130 mmHg (57.6 2.5 mmHg, mean S.E.) and PVP change was augmented during enflurane anesthesia (p<0.05). Enflurane anesthesia accentuated correlationship between mean arterial pressure and PVP. CONCLUSION: Our observation showed that peak PVP occurred during deflation phase and its range of variation was substantial. Changes in the pattern and the autoregulation of PVP by enflurane needs further investigation.

The Phantom Limb Sensation Expressed by Spinal Anesthesia / 대한마취과학회지

BACKGROUND: Phantom limb sensation is an unusual position sense of the extremity during nerve block that the position of extremity is misinterpreted as being flexed, or elevated, when actually they are in neutral position. Whether it is from the fixation of proprioceptive input at the time of motor blockade or from unmasking of the pattern which has been already present in the CNS is still controversial. We perfomed this study under the assumption that phantom limb sensation can still be reproduced without the influence of position at the time of nerve blockade. METHODS: Thirty-six patients scheduled for elective orthopedic surgery were randomly assigned. For 26 patients, spinal anesthesia was performed with hyperbaric 0.5% tetracaine or bupivacaine at lateral decubitus position and the position was changed to supine immediately. Existence of phantom limb sensation and the level of anesthesia was recorded at 10 and 20 minutes after injection of local anesthetics. For 10 patients, same local anesthetics were injected after patient's legs were straightened in lateral decubitus position. RESULTS: Forteen out of 26 patients whose position were changed to supine immediately after the injection of local anesthetics experienced phantom limb sensations. Five out of 10 patients whose legs were kept straight before the injection of local anesthetics experienced phantom limb sensations. Previous history of trauma was positively related to the expression of phantom limb sensation. CONCLUSION: Our data showed that the expression of phantom limb sensation is reproducible. And this was not related to the position at the time of spinal anesthesia. Trauma seems to be an important factor related to the expression of phantom limb sensation.

Effects of electrical stimulation of brainstem nuclei on dorsal horn neuron responses to mechanical stimuli in a rat model of neuropathic pain

The aim of the present study is to examine the brainstem sites where the electrical stimulation produces a suppression of dorsal horn neuron responses of neuropathic rats. An experimental neuropathy was induced by a unilateral ligation of L5-L6 spinal nerves of rats. Ten to 15 days after surgery, the spinal cord was exposed and single-unit recording was made on wide dynamic range (WDR) neurons in the dorsal horn. Neuronal responses to mechanical stimuli applied to somatic receptive fields were examined to see if they were modulated by electrical stimulation of various brainstem sites. Electrical stimulation of periaqueductal gray (PAG), n. raphe magnus (RMg) or n. reticularis gigantocellularis (Gi) significantly suppressed responses of WDR neurons to both noxious and non-noxious stimuli. Electrical stimulation of other brainstem areas, such as locus coeruleus. (LC) and n. reticularis paragigantocellularis lateralis (LPGi), produced little or no suppression. Microinjection of morphine into PAG, RMg, or Gi also produced a suppression as similar pattern to the case of electrical stimulation, whereas morphine injection into LC or LPGi exerted no effects. The results suggest that PAG, NRM and Gi are the principle brainstem nuclei involved in the descending inhibitory systems responsible for the control of neuropathic pain. These systems are likely activated by endogenous opioids and exert their inhibitory effect by acting on WDR neurons in the spinal cord.

The Effect of Thyrotropin Releasing Hormone on somatosensory Evoked Potentials in Cats with Spinal Cord Injury

The therapeutic goal for the spinal injury has been focused on preventing the secondary ischemic changes because of the poor regeneration of human spinal cord. Naloxone, an antagonist of endogenous opiates, has been clinically used for the purpose of preventing ischemic change and improving the recovery of neurological function after spinal injury. Recently, thyrotropin releasing hormone(TRH), a hypothalamic hormone inducing the thyrotropin secretion in anterior pituitary gland, has been known as a potent stimulator of cardiovascular functions in shock and the neurologic recovery in injuries of central nervous system, however, its underlying mechanism is still obscure. The present study was designed to determine whether TRH was also effective to improve the experimentally induced spinal injury as naloxone did, Somatosensory evoked potentials(SEPs) have used as an index for recovery of neurological function after the spinal injury which was induced by the 400gm.cm contusion of the T-7 spinal level in cats. The results are summarized as follows : 1. SEPs abolished soon after spinal contusion were reappeared 3 hours after injury when either of naloxone(10mg/kg) or TRH(4mg/kg) was administrated intravenously. Its recovery was completed after 24 hours. 2. The recovery rates of SEPs after treatments of naloxone and TRH were 62.5% and 64.7% of experimental animals, respectively. In conclusion, the present studies confirm the therapeutic benefit of TRH in experimental spinal injury and demonstrate that it is superior to treatment with naloxone. Further studies would be needed to explain the underlying mechanism of TRH effects.