Transcutaneous electrical nerve stimulation (TENS), acupuncture-needling, and electroacu! Puncture are useful non-ablative methods in medical practice for relief of acute and chronic r pain These procedures appear to work by causing an increased discharge in afferent nerve fibers which in turn modifies the transmission of impulses in pain pathways. The present study was performed to evaluate the analgesic effects of peripheral nerve stimulation with different stimulatory parameters in decerebrated cats and spinalized cats. And we studied the effects of naloxone, a specific opiate antagonist, on analgesia produced by 50 Hz, C intensity conditioning stimulation. The electrical response of.spinal neurons was elicited either by electrical stimulation of the ipsilateral common peroneal nerve or tibial nerve, and then the single unit activity of the dorsal horn cell was recorded with a carbon filament-filled glass microelectrode at the lumbosacral spinal cord. The conditioning stimuli which provoke the pain inhibitory mechanism were applied to the cornmon peroneal nerve or tibial nerve with a relatively high frequency (25, 50, 200Hz) for 15, 30, and 60 seconds at suprathreshold intensity for A delta or C fiber. The results of the experiment are summarized as follows: 1. Peripheral conditioning stimulation at C strength showed larger analgesic effects than those produced by stimulation at A delta strength. And analgesic effects produced by conditioning stimulation for 30sec were greater than those produced by stimulation for 15sec, but showed no statistically significant difference from those produced by stimulation for 60 sec. 2. Analgesic effects produced by 50Hz conditioning stimulation were greater than thoseproduced by 25Hz stimulation. But 200Hz stimulation showed a lesser analgesic effect than 50 or 25Hz conditioning stimulation. 3. The analgesic effect produced by 50Hz conditioning stimulation was only slightly affected by naloxone, a specific opiate antagonist, indicating that involvement of an endogenous opiate system was minimal. 4. The analgesic effect produced by conditioning stimulation in decerebrated cats was nearly the same as in spinal cats suggesting that the neural circuitry responsible for the analgesic action seems to reside mostly within the spinal cord. From the above results, it is concluded that 1) frequency of stimulation is important for an efficient analgesia, i.e., stimulation with excessively high frequency decreases the analgesic effect, 2) the analgesic effect produced by high frequency conditioning stimulation may be minimally mediated by an endogenous opiate system, and 3) the site of analgesic action resides mainly in the spinal cord.
Analgesia ; Animals ; Carbon ; Cats ; Electric Stimulation* ; Glass ; Microelectrodes ; Naloxone ; Nerve Fibers ; Nerve Fibers, Unmyelinated ; Neurons ; Peripheral Nerves* ; Peroneal Nerve ; Posterior Horn Cells* ; Punctures ; Spinal Cord ; Tibial Nerve ; Transcutaneous Electric Nerve Stimulation

An effect of D-phenylalanine on the pain inhibitory mechanism of prolonged electrical stimulation of the peripheral nerve was studied in decerebrate cats and spinal cats. The response of spinal neurons was elicited either by electrical stimulation of the ipsilateral common peroneal nerve and tibial nerve. The single-unit activity of motor neurons which represent the flexion reflex was recorded from a filament of ventral rootlet divided from either the L7, S1 or S2 ventral root, and activity of dorsal horns cells was recorded with a microelectrode at the lumbosacral cord The conditioning stimuli which provocate the pain inhibitory mechanism of the common peroneal or tibial nerve was applied with repetitive, low frequency (2Hz), at a suprathreshold intensity for C fiber, for 30-45 minutes. The results of the experiment are summarized as follows: 1. Applying conditioning stimuli produced a powerful inhibition of the responses which was provocated by noxious stimuli in either the decerebrate or the spinal cat without any statistical difference, and this effect can be observed for 15 minutes after the cessation of the conditioning stlmuli 2. This response was reversed completely by systemic injection of a specific opiate antagonist, naloxone. It suggests that the conditioning stimulus of the peripheral nerve can produce the endogenous opiate related pain inhibitory effect as the spinal mechanism. 3. The conditioning stimuli can produce the analgesic effect by means of supression of the activity of the dorsal horn cell which was related to the pain response in the decerebrate cat. The same result could be observed in flexion reflex. 4. D-phenylalanine, a putative inhibitor of carboxypeptidase which degradates the endogenous opiate-enkephalin, was studied in this experiment under the hypothesis that D-phenylalanine will emphasize or prolongate the action of enkephalin. But, intravenously injected D-phenylalanine did not potentiate the inhibitory effect of the conditioning stimuli of the peripheral nerve. From the above result, it is speculated that the electrical stimulation of the peripheral nerve is directly mediated by an endogenous opiate related analgesia, and the site of the analgesic action resides mainly in spinal cord level. But these data could not support the gypothesis that antinociceptive effect of D-phenylalanine results frm the potentiation of endogenously released enkephalin.
Analgesia* ; Animals ; Cats* ; Electric Stimulation ; Enkephalins ; Horns ; Microelectrodes ; Motor Neurons ; Naloxone ; Nerve Fibers, Unmyelinated ; Neurons ; Peripheral Nerves* ; Peroneal Nerve ; Posterior Horn Cells ; Reflex ; Spinal Cord ; Spinal Nerve Roots ; Tibial Nerve

Transcutaneous electrical nerve stimulation(TENS), acupuncture-needling, and electroacupuncture are useful non-ablative methods in medical practice for relief of pain. These procedures appear to work by causing an increased discharge in afferent nerve fibers which in turn modifies the transmission of impulses in pain pathways. It is known that the mechanism of analagesic effect via these maneuvers are variable depending on the stimulating parameters. For example, the endogenous opioid system is profoundly related to the mechanism when a peripheral nerve stimulation is applied with parameters of low frequency and high intensity. However, when stimulated with parameters of high frequency and high intensity, the reduced activity of dorsal horn neurons is only slightly reversed by a systemic administration of naloxone, a specific opiate antagonist. Thus, the present study was performed to investigate the neurotransmitter that concerns the mechanism of peripheral nerve stimulation with parameters of high frequency and high intensity. We used an iontophoretic application of antagonists of possible related neurotransmitters. The dorsal horn neuron activity which was evoked by squeezing the peripheral cutaneous receptive field, was recorded as an index of pain with a microelectrode at the lumbo-sacral spinal cord. Naloxone, picrotoxin and strychnine were applied at 200nA during a period of conditioning nerve stimulation. We observed the effects of these drugs on the change of dorsal horn neuron activities. The main results of the experiment can be summarized as follows. The spontaneous activity of dorsal horn neurons increased in the presence of glutamate and decreased with GABA. It did not change with naloxone, picrotoxin or strychnine. When naloxone was applied iontophoretically during peripheral nerve stimulation, there was no statistically significant analgesic effect compared with that of the control group. When picrotoxin was applied iontophoretically during peripheral nerve stimulation, the analgesic effect was reduced. When strychnine was applied, the analgesic effect was reduced but did not show a statistically significant difference with the control group. These results suggested that the GABAergic system may have been partially related in the analgesic action of peripheral nerve stimulation with parameters of high frequency and high intensity.
Animal ; Cats ; *Conditioning (Psychology) ; Female ; Iontophoresis ; Male ; Naloxone/*pharmacology ; Neurons/drug effects ; Picrotoxin/*pharmacology ; Spinal Cord/cytology/*drug effects ; Strychnine/*pharmacology ; *Transcutaneous Electric Nerve Stimulation

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 changes in extracellular calcium activities during contractures of guinea pig atrial trabecular muscles were measured with Ca2+-selective electrodes. When the tissue was superfused with Na+-free Tyrode solution extracellular Ca2+ activities were decreased and contractures were induced with some delay. When the contracture was relaxed with Na+-containing Tyrode solution, extracellular Ca2+ activities were increased transiently and recovered in a Na+-dependent manner. The magnitude of extracellular Ca2+ activity decreased was proportional to the maximum magnitude of contracture induced by Na+-free solution. Addition of caffeine (10 mM) to Na+-free solution induced transient contracture following slow development of contracture and an increase in extracellular Ca2+ activity. Removal of caffeine from Na+-free solution caused a slow relaxation of contracture and a decrease in extracellular Ca2+ activity. These results confirm that caffeine blocks Ca2+ uptake by the sarcoplasmic reticulum (SR) resulting in an increase in sarcoplasmic Ca2+ activity. Ca2+ activity in the extracellular space, the amount of Ca2+ transported into the cell(Ca2+ depletion in the extracellular space), and the magnitude of contracture are well correlated. Present experiments suggest that extracellular use of Ca2+-selective electrodes provides continuous and quantitative monitoring of Na+-dependent Ca2+ flux across the cardiac cell membrane.