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K F Shen

Publications and source records attributed to K F Shen.

35 records · Page 2Linked to original sources
PubMed1992

After chronic opioid exposure sensory neurons become supersensitive to the excitatory effects of opioid agonists and antagonists as occurs after acute elevation of GM1 ganglioside.

Mouse sensory dorsal-root ganglion (DRG) neurons chronically exposed to 1 microM D-Ala2-D-Leu5-enkephalin (DADLE) for greater than 1 week in culture become tolerant to opioid inhibitory effects, i.e. shortening of the duration of the calcium-dependent component of the action potential (APD). Acute application of higher concentrations of DADLE (ca. 10 microM) to these treated neurons not only fails to shorten the APD but, instead, generally elicits excitatory effects, i.e. prolongation of the APD. The present study shows that chronic DADLE- or morphine-treated DRG neurons also become supersensitive to the excitatory effects of opioids. Whereas nM concentrations of dynorphin(1-13) are generally required to prolong the APD of naive DRG neurons, fM levels become effective after chronic opioid treatment. Whereas 1-30 nM naloxone or diprenorphine do not alter the APD of naive DRG neurons, both opioid antagonists unexpectedly prolong the APD of most of the treated cells. Similar supersensitivity to the excitatory effects of opioid agonists and antagonists was previously observed after acute treatment of naive DRG neurons with GM1 ganglioside. Our results suggest that both chronic opioid and acute GM1 treatments of DRG neurons greatly enhance the efficacy of opioid excitatory receptor functions so that even the extremely weak agonist properties of naloxone and diprenorphine become effective in prolonging the APD of these treated cells when tested at low concentrations, whereas their antagonist properties at inhibitory opioid receptors do not appear to be altered. Furthermore, whereas cholera toxin-B subunit (CTX-B; 1-10 nM) blocks opioid-induced APD prolongation in naive DRG neurons (presumably by interfering with endogenous GM1 modulation of excitatory opioid receptors functions), even much higher concentrations of CTX-B were ineffective in chronic opioid-treated as well as acute GM1-elevated neurons. These and related data suggest that opioid excitatory supersensitivity in chronic opioid-treated DRG neurons may be due to a cyclic AMP-dependent increase in GM1 ganglioside levels. Our results may clarify mechanisms of opioid dependence and the paradoxical supersensitivity to naloxone which triggers withdrawal symptoms after opiate addiction.

Action Potentials↗
PubMed1992

After GM1 ganglioside treatment of sensory neurons naloxone paradoxically prolongs the action potential but still antagonizes opioid inhibition.

Low (nanomolar) concentrations of opioid agonists prolong the calcium-dependent component of the action potential duration (APD) of many dorsal root ganglion (DRG) neurons, whereas higher (micromolar) levels shorten the APD. Both effects are blocked by naloxone (1-10 nM). Opioid-induced APD prolongation appears to be mediated by excitatory opioid receptors that are positively coupled via a cholera toxin-A-sensitive Gs protein to adenylate cyclase/cyclic AMP-dependent ion conductances, whereas opioid-induced APD shortening is mediated by inhibitory receptors linked via pertussis toxin-sensitive Gi/Go proteins. Cholera toxin-B subunit, which binds to GM1 ganglioside, also selectively blocks opioid-induced APD prolongation. After brief treatment with GM1 ganglioside, the opioid agonists, dynorphin (1-13) or morphine, prolong the APD at femtomolar vs. the usual nanomolar concentrations, whereas no significant alterations were observed in the sensitivity of these GM1-treated cells to opioid inhibitory effects elicited by higher opioid concentrations. The present study shows that the opioid antagonists, naloxone or diprenorphine (1-30 nM), did not alter the APD of naive DRG neurons. In contrast, after GM1 treatment (1 microM, greater than 10 min), both opioid antagonists (but not (+)naloxone) unexpectedly prolonged the APD of most of the GM1-treated cells, but still continued to antagonize opioid-induced APD shortening. These results suggest that the supersensitivity of GM1-treated DRG neurons to the excitatory effects of opioid agonists and antagonists is due primarily to a remarkably increased efficacy of excitatory Gs-coupled opioid receptor functions, similar to the opioid excitatory supersensitivity that we have recently observed in chronic opioid-treated DRG neurons.

Action Potentials↗
PubMed1991

Brief treatment of sensory ganglion neurons with GM1 ganglioside enhances the efficacy of opioid excitatory effects on the action potential.

In previous studies, we showed that low (nM) concentrations of opioid prolong the action potential duration (APD) of many mouse dorsal root ganglion (DRG) neurons via Gs-linked excitatory opioid receptors, whereas micromolar opioid levels shorten the APD via Gi/Go-linked inhibitory receptors. In addition, cholera toxin-B subunit (CTX-B) selectively blocks opioid- but not forskolin-induced prolongation of the APD in DRG neurons. Since CTX-B binds with selective high affinity to GM1 ganglioside located on the cell surface, the results suggest that GM1 plays an essential role in regulating excitatory opioid receptor functions. This hypothesis was tested by treating DRG neurons in mouse DRG-cord explants with exogenous gangliosides and determining whether the efficacy of opioid agonists in prolonging the APD is enhanced. The threshold concentration of the opioids, dynorphin(1-13) and morphine required to prolong the APD in many DRG neurons was markedly decreased from nM to fM levels after bath exposure to 10 nM to 1 microM GM1 ganglioside for less than 5 min. In contrast, GM2 and GM3 gangliosides and asialo-GM1 ganglioside were ineffective, even when DRG neurons were exposed to high concentrations (1-10 microM) for periods greater than 1 h. Although GD1a, GD1b and GQ1b gangliosides appeared to be as effective as GM1 when tested at microM concentrations for 15 min, tests at lower concentrations, shorter periods, and/or at lower temperature (24 degrees vs 34 degrees C), showed that they were significantly less effective than GM1.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗
PubMed1991

Opioids at low concentration decrease openings of K+ channels in sensory ganglion neurons.

Previous studies showed that low concentrations of opioids prolong the calcium-dependent component of the action potential duration (APD) of dorsal root ganglion (DRG) neurons, whereas higher concentrations shorten the APD. In the present study whole-cell voltage-clamp, as well as cell-attached membrane-patch voltage-clamp, recordings demonstrate that application of picomolar to nanomolar concentrations of mu, delta or kappa opioid agonists (DAGO, DPDPE or dynorphin) to DRG neurons in dissociated cell cultures reversibly decreased the activities of voltage-sensitive K+ channels. Pretreatment of DRG neurons with the opioid receptor antagonists, naloxone (30 nM) or diprenorphine (1 nM) prevented mu/delta or kappa opioid-induced decreases in K+ channel activities, respectively. Since opioids added to the bath solution decreased the activities of K+ channels in the membrane patch sealed off by the pipette tip, our results provide strong evidence that some modes of excitatory modulation of the action potential of DRG neurons are mediated by diffusible second messengers. The data are consonant with our previous studies indicating that opioids can elicit excitatory effects on sensory neurons via cholera toxin-sensitive Gs-linked excitatory opioid receptors coupled to cyclic AMP-dependent ionic channels.

Action Potentials↗
PubMed1990

Cholera toxin-B subunit blocks excitatory effects of opioids on sensory neuron action potentials indicating that GM1 ganglioside may regulate Gs-linked opioid receptor functions.

In a previous study, we demonstrated that cholera toxin-A subunit, as well as the whole toxin, selectively blocks opioid-induced prolongation of the Ca2+ component of the action potential duration (APD) in dorsal root ganglion (DRG) neurons, indicating mediation of this excitatory effect by Gs-linked opioid receptors. The present study shows that pretreatment of DRG neurons with the B subunit of cholera toxin (1-10 ng/ml; greater than 15 min) can also block mu/delta and kappa opioid-induced APD prolongation, but not shortening. Since the B subunit binds selectively to GM1 ganglioside located on the cell surface, these results suggest that this ganglioside may regulate Gs-linked excitatory opioid receptor functions in DRG neurons. Possible contamination of purified B subunit preparations of cholera toxin with traces of the more potent A subunit was eliminated by heating the stock solution to 56 degrees C for 20 min. Exposure of DRG neurons to an affinity-purified anti-GM1 antiserum also blocked opioid-induced APD prolongation, providing further evidence that GM1 ganglioside may play an essential role in excitatory opioid modulation of the action potential of these cells. The blockade by cholera toxin-B subunit and anti-GM1 antibodies of opioid-induced APD prolongation is best accounted for by the following hypothesis: CTX-B interferes with an endogenous GM1 ganglioside component of the excitatory, but not inhibitory, opioid receptor complex on DRG neurons that may allosterically regulate coupling of the receptors via Gs to adenylate cyclase/cyclic adenosine monophosphate-dependent ionic conductances.

Action Potentials↗
PubMed1990

Cholera toxin-A subunit blocks opioid excitatory effects on sensory neuron action potentials indicating mediation by Gs-linked opioid receptors.

Our previous studies indicated that opioid-induced prolongation of the Ca2+ component of the action potential duration (APD) in dorsal root ganglion (DRG) neurons is mediated by excitatory opioid receptors that are coupled to cyclic AMP-dependent voltage-sensitive ionic conductances. In the present study, DRG neurons were treated with cholera toxin (CTX), or with the A subunit of CTX, in order to determine if these excitatory opioid receptors are positively coupled via the GTP-binding protein Gs to the adenylate cyclase/cyclic AMP system. In contrast, inhibitory opioid receptors have been shown to be linked to pertussis toxin-sensitive Gi/Go regulatory proteins that mediate APD shortening responses. After pretreatment of DRG-spinal cord explants with remarkably low concentrations of CTX-A (1 pg/ml-1 ng/ml; greater than 15 min) or whole toxin (1 pg/ml-1 microgram/ml) the APD prolongation elicited in DRG neurons by 1-10 nM delta/mu (DADLE) or kappa (U-50,488H) opioids was blocked (29 out of 30 cells), whereas APD shortening by microM opioid concentrations was unaffected. Opioid-induced APD prolongation was blocked even when the initial treatment with CTX or CTX-A alone did not prolong the APD. The blocking effects of CTX and CTX-A were reversed in tests made 2 h after return to control medium. The mechanisms underlying the unusually potent blocking effects of CTX and CTX-A on opioid excitatory modulation of the APD of DRG neurons require correlative biochemical analyses.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗
PubMed1990

Opioids can evoke direct receptor-mediated excitatory effects on sensory neurons.

Activation of opioid receptors has generally been considered to produce inhibitory effects on neuronal activity. However, recent studies indicate that specific mu-, delta- and kappa-opioid receptor agonists can elicit excitatory, as well as inhibitory, modulation of the action potentials of sensory neurons isolated in culture. Stanley Crain and Ke-Fei Shen review the evidence for mediation of these direct excitatory effects by naloxone-reversible opioid receptors. They propose that this dual modulatory mechanism may help to account for previously unexplained enhancement by opioids of transmitter release, paradoxical hyperalgesic and aversive effects of opioids, and some aspects of opioid tolerance and addiction.

Humans↗
PubMed1990

Dynorphin prolongs the action potential of mouse sensory ganglion neurons by decreasing a potassium conductance whereas another specific kappa opioid does so by increasing a calcium conductance.

Previous studies have reported that large (microM) concentrations of kappa opioids, e.g. dynorphin and 3,4 dichloro-N-methyl-N-(2-[1-pyrrolidinyl]-cyclohexyl)benzene-acetamide (U-50,488H), shorten the duration of the calcium component of the action potential of dorsal root ganglion neurons by decreasing a voltage-sensitive Ca2+ conductance. The present study showed that, in addition to these inhibitory modulatory effects, small (nM) concentrations of dynorphin, as well as U-50,488H, prolonged the action potential in about 75% of the neurons of dorsal root ganglia in ganglion spinal cord explants of mouse (tested in 5 mM Ba2+). Both the excitatory and inhibitory effects of these kappa opioids were prevented by perfusion together with the opioid antagonist, diprenorphine (10 nM). However, when responsivity tests with opioids were carried out in the presence of multiple K+ channel blockers [Ba2+, Cs+ and tetraethylammonium (TEA)], 1 nM dynorphin prolonged the action potential in only 7% of the neurons (n = 28), whereas 1 nM U-50,488H still elicited the prolongation of the action potential in 60% of the cells (n = 39). These data suggest that dynorphin prolongs the action potential of neurons of dorsal root ganglion by activating a kappa subtype of receptor that decreases a voltage-sensitive K+ conductance, whereas U-50,488H produces similar excitatory modulation of the action potential by activating another kappa subtype of receptor that increases a voltage-sensitive Ca2+ conductance. Thus, U-50,488H-induced prolongation of the action potential appears to be mediated by a kappa subtype of receptor that produces the opposite effect on Ca2+ channels to that which occurs during kappa opioid-induced shortening of the action potential.(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1989

Dual opioid modulation of the action potential duration of mouse dorsal root ganglion neurons in culture.

Multiple modulatory effects of opioids on the duration of the calcium component of the action potential (APD) of dorsal-root ganglion (DRG) neurons of mouse spinal cord-ganglion explants were studied. The APD of DRG neuron perikarya has been previously shown to be shortened by exposure to high concentrations of opioids (ca. 0.1-1 microM) in about 1/2 of the cells tested. The present study demonstrates that in addition to these inhibitory modulatory effects of opioids, lower concentrations (1-10 nM) of present study demonstrates that in addition to these inhibitory modulatory effects of opioids, lower concentration (1-10 nM) of delta- mu, and kappa-opioid agonists elicit excitatory modulatory effects, i.e. prolongation of the APD, in about 2/3 of the sensory neurons tested. APD prolongation as well as shortening elicited by delta, mu, and kappa agonists were prevented by coperfusion with the opioid antagonists, naloxone or diprenorphine (10 nM). APD prolongation induced by the delta-agonist [D-Ala2-D-Leu5]enkephalin (DADLE) was prevented in the presence of multiple K+ channel blockers, whereas excitatory modulation by the specific kappa-agonist, U-50,488H was not attenuated under these conditions. After treatment of DRG neurons with pertussis toxin (1 micrograms/ml for several days) or forskolin (50 muM for less than 15 min), a much smaller fraction of cells showed opioid-induced APD shortening; moreover, a much larger fraction of cells showed opioid-induced APD prolongation, even when tested with high concentrations of DADLE (1-10 muM). These data indicate that opioid-induced APD prolongation is not mediated by pertussis toxin-sensitive G proteins (which have been shown to regulate opioid inhibitory effects) and suggest that elevation of cyclic AMP levels may enhance opioid excitatory responsiveness. Furthermore, our analyses indicate that mu-, delta- and kappa-subtypes of excitatory as well as inhibitory opioid receptors may be expressed on the same DRG neuron perikaryon under in vitro conditions. If dual opioid modulation of the APD of DRG perikarya also occurs in central DRG terminals this may play a significant role both in nociceptive signal transmission as well as tolerance to opioid analgesia.

Action Potentials↗
PubMed1988

Effects of temperature alterations on population and cellular activities in hippocampal slices from mature and immature rabbit.

Effects of temperature on population spike and cellular activities have been assessed in the CA1 region of hippocampal slices from mature and immature rabbit. In field potential recordings, population spike amplitude was maximal at near 30 degrees C for both mature and immature tissue, and fell off as temperature was either raised (to a maximum of 44 degrees C) or lowered (to a minimum of 20 degrees C). With cooling below 30 degrees C, population spikes decreased in amplitude and became broader; stimuli always elicited some response, and changes due to cooling were reversible. With increases in temperature, however, irreversible decrease and/or loss of population spikes occurred when tissue was warmed beyond 43 degrees C. Input-output curves established for mature and immature slices indicated that, at all temperatures, population spike amplitude grew more rapidly with small increases in stimulus intensity in immature slices as compared to mature slices. Intracellular recordings were made from CA1 pyramidal cells in mature and immature hippocampal slices. For both mature and immature tissues, moderate warming (to 40 degrees C) produced membrane hyperpolarizations in many cells, especially in the mature hippocampus. Increasing temperature beyond 40 degrees C led to marked depolarizations in a number of cells, a depolarization that was irreversible, particularly in mature neurons. Cooling generally produced a depolarizing shift in membrane potential and an accompanying increase in input resistance; these effects, however, were reversible. Temperature changes in both warming and cooling directions had effects on repetitive firing patterns in both mature and immature neurons. In particular, spike trains elicited by a constant current pulse at a given membrane potential became shorter. The effects of cooling on this cell parameter were reversible, but warming-induced changes were usually permanent. Irreversibility of the warming effects was more pronounced in cells from mature than from immature hippocampus. As reported previously, cooling produced marked spike broadening and changes in synaptic potentials in both mature and immature neurons. These studies confirm previously reported temperature sensitivities of neuronal properties in hippocampal slices. On the basis of these data, and reports from other laboratories, it is clear that relatively small changes in temperature can have rather dramatic effects on properties of single cells and cell populations. Such temperature sensitivity is critical in evaluating data obtained from in vitro slice preparations.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗
PubMed1988

Inhibitor of cyclic AMP-dependent protein kinase blocks opioid-induced prolongation of the action potential of mouse sensory ganglion neurons in dissociated cell cultures.

The duration of the calcium component of the action potential (APD) of dorsal root ganglion (DRG) neurons in mouse spinal cord-ganglion explants has been shown to be dually modulated via excitatory and inhibitory opioid receptors. In order to determine if opioid-induced APD prolongation is modulated by receptors that are positively coupled to the adenylate cyclase (AC)/cyclic AMP second messenger system, whole-cell recordings were made from mouse DRG neurons grown in dissociated cell cultures. Tests for opioid responsivity were carried out after intracellular dialysis of an inhibitor of cAMP-dependent protein kinase (PKI). In control recordings, both DADLE-induced APD prolongation as well as shortening were prevented by co-perfusion with the opioid antagonist, diprenorphine (10 nM). Intracellular dialysis of PKI in these neurons completely blocked opioid-induced APD prolongation but did not attenuate APD shortening generally elicited by higher opioid concentrations. Bath perfusion of 10 nM DADLE elicited APD prolongation in 59% of the DRG neurons (n = 34) tested with control solution in the recording pipette, whereas none showed APD prolongation when the pipette contained PKI (n = 18). In control tests with 1 microM DADLE, the APD was prolonged in 37% of the cells and shortened in 26% (n = 19); in contrast, a matched group of PKI-treated cells showed no APD prolongation, whereas 42% showed APD shortening (n = 26). The results support the hypothesis that opioid-induced APD prolongation in DRG neurons is mediated by opioid receptor subtypes that are positively coupled via Gs to AC/cAMP-dependent voltage-sensitive ionic conductances.

Action Potentials↗
PubMed1988

Opioids excite rather than inhibit sensory neurons after chronic opioid exposure of spinal cord-ganglion cultures.

Tests were carried out to determine if the tolerance that develops in dorsal-horn network responses of mouse dorsal root ganglion (DRG)-spinal cord explants after chronic exposure to opioids could be accounted for by alterations in the excitability and pharmacologic properties of the afferent DRG cells. Intracellular recordings were made from DRG neurons in organotypic DRG-cord explants after chronic treatment with 1 microM D-Ala2-D-Leu5-enkephalin (DADLE) for greater than 4 days in vitro. Acute application of 10 microM DADLE shortened the duration of the Ca2+ component of the somatic action potential (APD) in only 5% of the treated neurons (4 out of 79 cells), in contrast to about 50% of the cells in naive explants (36 out of 74). Thus many DRG neuron perikarya became tolerant to the APD-shortening effects of DADLE. Furthermore, 77% of the treated DRG cells (61 out of 79) showed prolongation of the APD in response to an acute increase in DADLE concentration vs 34% in naive explants (25 out of 74). However, when the DADLE responsivity tests were carried out in the presence of multiple K+ channel blockers, only 20% of the treated DRG neurons showed APD prolongation (3 out of 15 cells), whereas 73% showed APD-shortening responses (11 out of 15 cells). The results suggest that: (1) DADLE-induced APD prolongation of the treated DRG neurons is mediated by opioid receptor subtypes that decrease a voltage-sensitive K+ conductance; (2) the DADLE-induced APD-shortening effects which are unmasked during more complete K+ channel blockade are mediated by opioid-receptor subtypes in the same neuron that reduce a voltage-sensitive Ca2+ conductance (resembling kappa receptors). DRG neurons did not become tolerant to either of these two opioid effects after chronic exposure to DADLE. Opioid shortening of the APD of DRG neuron perikarya has been generally accepted to be a model of opioid inhibition of calcium influx and transmitter release at presynaptic DRG terminals6,52,53,65,75,76. It is postulated that the opioid-induced APD prolongation observed in the present study provides evidence that opioids can also evoke direct excitatory effects on neurons. The enhancement of DADLE-induced excitatory responses and attenuation of DADLE-induced inhibitory responses of DRG neurons after chronic exposure to this opioid show striking similarities to the effects of forskolin or pertussis toxin treatment. These in vitro studies may provide clues to compensatory mechanisms underlying physiologic expression of tolerance to opioid analgesic effects in primary afferent synaptic networks.

Action Potentials↗
PubMed1986

Organization of synaptic transmission in the mammalian solitary complex, studied in vitro.

1. Synaptic transmission and neuronal morphology were studied in the nucleus tractus solitarius and in the dorsal vagal motor nucleus (solitary complex), in coronal brain-stem slices of rat or cat, superfused in vitro. 2. Electrical stimulation of afferent fibres of the solitary tract evoked two different types of post-synaptic response recorded intracellularly in different solitary complex neurones. Labelling with horseradish peroxidase showed that these two sorts of orthodromically evoked responses were correlated with different post-synaptic neuronal morphologies. 3. The majority of recorded neurones (n = 93) showed a prolonged reduction in excitability following the initial solitary-tract-evoked excitatory post-synaptic potential (e.p.s.p.). A smaller number of neurones (n = 53) showed a prolonged increase in excitability following solitary tract stimulation. In no case did the solitary tract stimulation induce a burst of action potentials at high frequency. 4. The time-to-peak and the half-width of the initial solitary-tract-evoked e.p.s.p. were shorter in neurones with prolonged increased excitability than in those with prolonged reduced excitability. In neurones with prolonged reduced excitability, this e.p.s.p. was followed by a hyperpolarization lasting 60-100 ms. The latency of this inhibitory post-synaptic potential (i.p.s.p.) was 3-5 ms longer than that of the initial e.p.s.p. and its reversal potential was 10 mV more negative than the reversal potential of the response measured following application of gamma-aminobutyric acid or glycine. In neurones with prolonged increased excitability, at a membrane potential of -40 to -50 mV, the initial solitary tract e.p.s.p. was followed by a prolonged depolarization lasting 100-400 ms. 5. Background synaptic activity was high in neurones with prolonged increased excitability, consisting of unitary e.p.s.p.s with an amplitude of more than 0.8 mV. This activity was increased for a period of 300-800 ms following solitary tract stimulation. Spontaneous excitatory potentials of more than 0.5 mV were not seen in neurones with prolonged reduced excitability. In these neurones, after intracellular injection of choride ions, reversed unitary i.p.s.p.s formed a background activity which was increased following stimulation of the solitary tract. 6. Neurones with prolonged reduced excitability were found in the medial, ventral and ventrolateral part of the nucleus tractus solitarius and in the dorsal vagal motor nucleus where they were identified by their antidromic response to stimulation ventral and lateral to the tractus solitarius.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗
PubMed1984

[Role of the hippocampus, amygdala and the substantia nigra in the evolution of status epilepticus induced by systemic injection of kainic acid in the rat].

The effects of bilateral microinjection of gamma-vinyl GABA (GVG, an irreversible inhibitor of GABA-T) were tested during the development of seizures induced by i.p. administration of 10 mg/kg of kainic acid. Intrahippocampal injection of GVG prevents the development of the seizures at an early stage in about half of the cases. In the remaining animals status epilepticus comparable to that of controls develops. Intra-amygdaloid injection reduces the severity of the seizures from the first motor limbic signs. Finally, intranigral injection prevents the appearance of convulsive status epilepticus or, when it develops, reduces its duration. The role that these three structures could play in the electro-clinical development of kainic acid-induced seizures is discussed.

Amygdala↗
PubMedDate not supplied

Effect of stimulation of bulbar reticular formation on long latency discharges in the region of nucleus centralis lateralis of thalamus.

Electrical stimulation of medial medullary reticular formation of rabbits was found to have marked inhibitory effect on nociceptive discharges of neurons in the region of centrolateral nucleus of thalamus. Among the 32 nociceptive units tested, 15 showed the inhibitory effect, 3 the facilitatory, and 14 no effect. Comparison between the effect of direct stimulation of medial medullary reticular formation and that of the electric needling on the same neurons revealed a general resemblance of the two in many respects. These findings suggest that the nucleus reticularis gigantocellularis in medial bulbar reticular formation may serve as an important relay station in the transmission of the analgesic effect of acupuncture.

Acupuncture Therapy↗