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*

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: 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*

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