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.
Anesthesia ; Anesthesia, Spinal* ; Anesthetics, Local ; Bupivacaine ; Extremities ; Humans ; Leg ; Nerve Block ; Orthopedics ; Phantom Limb* ; Proprioception ; Sensation* ; Tetracaine

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.
Animals ; Axons ; Chemokine CCL3 ; Chemokine CCL5 ; Diagnosis-Related Groups ; Ganglia, Spinal ; Hyperalgesia ; Ligation ; Neuralgia ; Nociceptors ; Peripheral Nerve Injuries ; Peripheral Nerves ; Rats ; Receptors, CCR1 ; Sciatic Nerve ; Skin ; Spinal Nerves ; Up-Regulation ; Wallerian Degeneration

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.
Animals ; Cats* ; Central Nervous System ; Contusions ; Evoked Potentials, Somatosensory* ; Humans ; Naloxone ; Opioid Peptides ; Pituitary Gland, Anterior ; Regeneration ; Shock ; Spinal Cord Injuries* ; Spinal Cord* ; Spinal Injuries ; Thyrotropin* ; Thyrotropin-Releasing Hormone*

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.
Animal ; Male ; Nerve Fibers/physiology* ; Nociceptors/physiology* ; Norepinephrine/pharmacology ; Pain/physiopathology* ; Rats ; Rats, Sprague-Dawley ; Receptors, Adrenergic, alpha-1/physiology*

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.
Adult ; Anesthesia* ; Arm ; Arterial Pressure ; Blood Pressure* ; Enflurane* ; Homeostasis ; Humans ; Venous Pressure* ; Volunteers

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.
Adult ; Animals ; Baclofen ; Carbon ; GABA Agonists ; gamma-Aminobutyric Acid ; Glass ; Hair ; Horns ; Humans ; Hyperalgesia ; Male ; Microelectrodes ; Muscimol ; Neurons ; Posterior Horn Cells ; Rats, Sprague-Dawley ; Spinal Cord Injuries* ; Spinal Cord*

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.
Action Potentials ; Animals ; Dizocilpine Maleate ; Electric Stimulation ; Glutamic Acid* ; Hyperalgesia* ; Neuralgia ; Peripheral Nerve Injuries ; Rats* ; Receptors, Glutamate* ; Rhizotomy* ; Spinal Nerves*

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.
Animals ; Back Pain ; Baclofen ; Bicuculline ; GABA-A Receptor Agonists ; GABA-A Receptor Antagonists ; GABA-B Receptor Agonists ; gamma-Aminobutyric Acid ; Ganglia, Spinal ; Hyperalgesia ; Hypersensitivity* ; Muscimol ; Neuralgia ; Posterior Horn Cells ; Rats* ; Receptors, GABA ; Spinal Cord

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). RESULTS: There was no statistical difference between different doses of DEX including the placebo. Rather, there was a tendency that DEX increases the pain. And there also was a tendency that average time to reach unbearable pain was decreased by DEX (P > 0.05). CONCLUSIONS: DEX is not effective in controlling tourniquet pain in normal awake subjects.
Acclimatization ; Arterial Pressure ; Central Nervous System Sensitization ; Chronic Pain ; Dextromethorphan* ; Extremities ; Healthy Volunteers* ; Heart Rate ; Humans ; Inflation, Economic ; Ischemia ; Male ; Models, Animal ; N-Methylaspartate ; Respiratory Rate ; Tourniquets* ; Volunteers

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.
Animal ; Calcitonin Gene-Related Peptide/pharmacology* ; Calcitonin Gene-Related Peptide/administration & dosage ; Excitatory Amino Acid Agonists/pharmacology* ; Iontophoresis ; Male ; N-Methylaspartate/pharmacology ; Rats ; Rats, Sprague-Dawley ; Spinal Cord/physiology ; Spinal Cord/drug effects* ; Substance P/pharmacology* ; Substance P/administration & dosage ; alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid/pharmacology