Modeling Long-term Spike Frequency Adaptation in SA-I Afferent Neurons Using an Izhikevich-based Biological Neuron Model

To develop a biomimetic artificial tactile sensing system capable of detecting sustained mechanical touch, we propose a novel biological neuron model (BNM) for slowly adapting type I (SA-I) afferent neurons. The proposed BNM is designed by modifying the Izhikevich model to incorporate long-term spike frequency adaptation. Adjusting the parameters renders the Izhikevich model describing various neuronal firing patterns. We also search for optimal parameter values for the proposed BNM to describe firing patterns of biological SA-I afferent neurons in response to sustained pressure longer than 1-second. We obtain the firing data of SA-I afferent neurons for six different mechanical pressure ranging from 0.1 mN to 300 mN from the ex-vivo experiment on SA-I afferent neurons in rodents. Upon finding the optimal parameters, we generate spike trains using the proposed BNM and compare the resulting spike trains to those of biological SA-I afferent neurons using the spike distance metrics. We verify that the proposed BNM can generate spike trains showing long-term adaptation, which is not achievable by other conventional models. Our new model may offer an essential function to artificial tactile sensing technology to perceive sustained mechanical touch.

Autoantibody-Mediated Dysfunction of Salivary Glands Leads to Xerostomia in SKG Mice

Sjögren's syndrome (SS) is a chronic heterogeneous disease that mainly affects exocrine glands, leading to sicca syndromes such as xerostomia. Despite the second highest prevalence rate among systemic autoimmune diseases, its pathophysiology remains largely unknown. Here we report that SKG mice, a cardinal model of Th17 cell-mediated arthritis, also develop a secondary form of SS-like disorder upon systemic exposure to purified curdlan, a type of β-glucan. The reduced production of saliva was not caused by focal immune cell infiltrates but was associated with IgG deposits in salivary glands. Sera from curdlan-injected SKG mice contained elevated titers of IgG (predominantly IgG1), autoantibody to the muscarinic type 3 receptor (M3R) and inhibited carbachol-induced Ca2+ signaling in salivary acinar cells. These results suggest that the Th17 cells that are elicited in SKG mice promote the production of salivary gland-specific autoantibodies including anti-M3R IgG; the antibodies are then deposited on acinar cells and inhibit M3R-mediated signaling required for salivation, finally leading to hypofunction of the salivary glands. This type II hypersensitivity reaction may explain the origin of secondary SS occurring without focal leukocyte infiltrates.

Antipruritic effect of curcumin on histamine-induced itching in mice

Itching is a common clinical symptom of skin disease that significantly affects a patient's quality of life. Transient receptor potential vanilloid 1 (TRPV1) receptors of keratinocytes and peripheral nerve fibers in skin are involved in the regulation of itching as well as pain. In this study, we investigated whether curcumin, which acts on TRPV1 receptors, affects histamine-induced itching in mice, using behavioral tests and electrophysiological approaches. We found that histamine-induced itching was blocked by topical application of curcumin in a concentration-dependent manner. In ex-vivo recordings, histamine-induced discharges of peripheral nerves were reduced by the application of curcumin, indicating that curcumin acts directly on peripheral nerves. Additionally, curcumin blocked the histamine-induced inward current via activation of TRPV1 (curcumin IC₅₀=523 nM). However, it did not alter chloroquine-induced itching behavior in mice, which is associated with transient receptor potential ankyrin 1 (TRPA1). Taken together, our results suggest that histamine-induced itching can be blocked by topical application of curcumin through the inhibitory action of curcumin on TRPV1 receptors in peripheral nerves.

Capsaicin upregulates HDAC2 via TRPV1 and impairs neuronal maturation in mice

Transient receptor potential vanilloid 1 (TRPV1) affects mood and neuroplasticity in the brain, where its role is poorly understood. In the present study we investigated whether capsaicin (8-methyl-N-vanillyl-trans-6-nonenamide), an agonist of TRPV1, induced chromatin remodeling and thereby altered gene expression related to synaptic plasticity. We found that capsaicin treatment resulted in upregulation of histone deacetylase 2 (HDAC2) in the mouse hippocampus and HDAC2 was enriched at Psd95, synaptophysin, GLUR1, GLUR2 promoters. Viral-mediated hippocampal knockdown of HDAC2 induced expression of Synapsin I and prevented the detrimental effects of capsaicin on Synapsin I expression in mice, supporting the role of HDAC2 in regulation of capsaicin-induced Synapsin I expression. Taken together, our findings implicate HDAC2 in capsaicin-induced transcriptional regulation of synaptic molecules and support the view that HDAC2 is a molecular link between TRPV1 activity and synaptic plasticity.

DAMGO modulates two-pore domain K⁺ channels in the substantia gelatinosa neurons of rat spinal cord

The analgesic mechanism of opioids is known to decrease the excitability of substantia gelatinosa (SG) neurons receiving the synaptic inputs from primary nociceptive afferent fiber by increasing inwardly rectifying K⁺ current. In this study, we examined whether a µ-opioid agonist, [D-Ala2,N-Me-Phe4, Gly5-ol]-enkephalin (DAMGO), affects the two-pore domain K⁺ channel (K2P) current in rat SG neurons using a slice whole-cell patch clamp technique. Also we confirmed which subtypes of K2P channels were associated with DAMGO-induced currents, measuring the expression of K2P channel in whole spinal cord and SG region. DAMGO caused a robust hyperpolarization and outward current in the SG neurons, which developed almost instantaneously and did not show any time-dependent inactivation. Half of the SG neurons exhibited a linear I~V relationship of the DAMGO-induced current, whereas rest of the neurons displayed inward rectification. In SG neurons with a linear I~V relationship of DAMGO-induced current, the reversal potential was close to the K⁺ equilibrium potentials. The mRNA expression of TWIK (tandem of pore domains in a weak inwardly rectifying K⁺ channel) related acid-sensitive K⁺ channel (TASK) 1 and 3 was found in the SG region and a low pH (6.4) significantly blocked the DAMGO-induced K⁺ current. Taken together, the DAMGO-induced hyperpolarization at resting membrane potential and subsequent decrease in excitability of SG neurons can be carried by the two-pore domain K⁺ channel (TASK1 and 3) in addition to inwardly rectifying K⁺ channel.

Fatal Clinical Course of Probable Invasive Pulmonary Aspergillosis with Influenza B Infection in an Immunocompetent Patient / 결핵및호흡기질환

Invasive pulmonary aspergillosis (IPA) is rarely reported in patients who have normal immune function. Recently, IPA risk was reported in nonimmunocompromised hosts, such as patients with chronic obstructive pulmonary disease and critically ill patients in intensive care units. Moreover, influenza infection is also believed to be associated with IPA among immunocompetent patients. However, most reports on IPA with influenza A infection, including pandemic influenza H1N1, and IPA associated with influenza B infection were scarcely reported. Here, we report probable IPA with a fatal clinical course in an immunocompetent patient with influenza B infection. We demonstrate IPA as a possible complication in immunocompetent patients with influenza B infection. Early clinical suspicion of IPA and timely antifungal therapy are required for better outcomes in such cases.

Retraction: A Novel Carbamoyloxy Arylalkanoyl Arylpiperazine Compound (SKL-NP) Inhibits Hyperpolarization-Activated Cyclic Nucleotide-Gated (HCN) Channel Currents in Rat Dorsal Root Ganglion Neurons

No abstract available.

A Novel Carbamoyloxy Arylalkanoyl Arylpiperazine Compound (SKL-NP) Inhibits Hyperpolarization-Activated Cyclic Nucleotide-Gated (HCN) Channel Currents in Rat Dorsal Root Ganglion Neurons

In this study, we determined mode of action of a novel carbamoyloxy arylalkanoyl arylpiperazine compound (SKL-NP) on hyperpolarization-activated cyclic nucleotide-gated (HCN) channel currents (Ih) that plays important roles in neuropathic pain. In small or medium-sized dorsal root ganglion (DRG) neurons (<40 microm in diameter) exhibiting tonic firing and prominent Ih, SKL-NP inhibited Ih and spike firings in a concentration dependent manner (IC50=7.85 microM). SKL-NP-induced inhibition of Ih was blocked by pretreatment of pertussis toxin (PTX) and N-ethylmaleimide (NEM) as well as 8-Br-cAMP, a membrane permeable cAMP analogue. These results suggest that SKL-NP modulates Ih in indirect manner by the activation of a Gi-protein coupled receptor that decreases intracellular cAMP concentration. Taken together, SKL-NP has the inhibitory effect on HCN channel currents (I h) in DRG neurons of rats.

Neurochemical Properties of Dental Primary Afferent Neurons

The long belief that dental primary afferent (DPA) neurons are entirely composed of nociceptive neurons has been challenged by several anatomical and functional investigations. In order to characterize non-nociceptivepopulation among DPA neurons, retrograde transport fluorescent dye was placed in upper molars of rats and immunohistochemical detection of peripherin and neurofilament 200 in the labeled trigeminal ganglia was performed. As the results, majority ofDPA neurons were peripherin-expressing small-sized neurons, showing characteristic ofnociceptive C-fibers. However, 25.7% of DPA were stained with antibody against neurofilament 200, indicating significant portion of DPA neurons are related to large myelinated Abeta fibers. There were a small number of neurons thatexpressed both peripherin and neurofilament 200, suggestive of Adelta fibers. The possible transition of neurochemical properties by neuronal injury induced by retrograde labeling technique was ruled out by detection of minimal expression of neuronal injury marker, ATF-3. These results suggest that in addition to the large population of C-fiber-related nociceptive neurons, a subset of DPA neurons is myelinated large neurons, which is related to low-threshold mechanosensitive Abeta fibers. We suggest that these Abeta fiber-related neurons might play a role as mechanotransducers of fluid movement within dentinal tubules.

Involvement of Crosstalk Between cAMP and cGMP in Synaptic Plasticity in the Substantia Gelatinosa Neurons

Substantia gelatinosa (SG) neurons receive synaptic inputs from primary afferent Adelta- and C-fibers, where nociceptive information is integrated and modulated by numerous neurotransmitters or neuromodulators. A number of studies were dedicated to the molecular mechanism underlying the modulation of excitability or synaptic plasticity in SG neurons and revealed that second messengers, such as cAMP and cGMP, play an important role. Recently, cAMP and cGMP were shown to downregulate each other in heart muscle cells. However, involvement of the crosstalk between cAMP and cGMP in neurons is yet to be addressed. Therefore, we investigated whether interaction between cAMP and cGMP modulates synaptic plasticity in SG neurons using slice patch clamp recording from rats. Synaptic activity was measured by excitatory post-synaptic currents (EPSCs) elicited by stimulation onto dorsal root entry zone. Application of 1 mM of 8-bromoadenosine 3,5-cyclic monophosphate (8-Br-cAMP) or 8-bromoguanosine 3,5-cyclic monophosphate (8-Br-cGMP) for 15 minutes increased EPSCs, which were maintained for 30 minutes. However, simultaneous application of 8-Br-cAMP and 8-Br-cGMP failed to increase EPSCs, which suggested antagonistic cross-talk between two second messengers. Application of 3-isobutyl-1-methylxanthine (IBMX) that prevents degradation of cAMP and cGMP by blocking phosphodiesterase (PDE) increased EPSCs. Co-application of cAMP/cGMP along with IBMX induced additional increase in EPSCs. These results suggest that second messengers, cAMP and cGMP, might contribute to development of chronic pain through the mutual regulation of the signal transduction.

The effects of midazolam and sevoflurane on the GABAA receptors with alternatively spliced variants of the gamma2 subunit / 대한마취과학회지

BACKGROUND: Emergence agitation after sevoflurane anesthesia in children can be prevented by midazolam. Alternative splicing of the GABAA receptor changes with age. Therefore, we hypothesized that alternative splicing of the gamma2 subunit affects the GABA current when applying sevoflurane and midazolam. METHODS: We performed the whole-cell patch clamp technique on human embryonic kidney 293 cells that were transfected with alpha1beta2gamma2L or alpha1beta2gamma2S. The concentration-response relations were recorded for midazolam and sevoflurane, and the co-application responses were measured at concentrations of 1.5 nM, 15 nM and 300 nM of midazolam and 0.5%, 2.0% and 4.0% of sevoflurane. Each GABA current was compared with that produced by 5 microM of GABA. RESULTS: The concentration-response relationships for midazolam and sevoflurane were dose-dependent without any differences between the alpha1beta2gamma2L and alpha1beta2gamma2S subtypes. 1.5 nM and 15 nM of midazolam did not significantly enhance the current after treatment with 0.5% sevoflurane for both subtypes. The current after treatment with 2.0% sevoflurane was enhanced by 1.5 nM midazolam for the alpha1beta2gamma2S subtype, but not for the alpha1beta2gamma2L subtype. In the case of 2.0% sevoflurane with 15 nM of midazolam, and 4.0% sevoflurane with 300 nM of midazolam, the GABA currents were significantly enhanced for both subtypes. CONCLUSIONS: These results show that the difference in the gamma2 subunit cannot explain the emergence agitation after sevoflurane anesthesia in children in vitro. This suggests that co-application of sevoflurane and midazolam enhances the GABA current according to the alternative splicing of the gamma2 subunit and the concentration of both drugs.

R-type Calcium Channel Isoform in Rat Dorsal Root Ganglion Neurons

R-type Cav2.3 high voltage-activated Ca2+ channels in peripheral sensory neurons contribute to pain transmission. Recently we have demonstrated that, among the six Cav2.3 isoforms (Cav2.3a~Cav2.3e), the Cav2.3e isoform is primarily expressed in trigeminal ganglion (TG) nociceptive neurons. In the present study, we further investigated expression patterns of Cav2.3 isoforms in the dorsal root ganglion (DRG) neurons. As in TG neurons, whole tissue RT-PCR analyses revealed the presence of two isoforms, Cav2.3a and Cav2.3e, in DRG neurons. Single-cell RT-PCR detected the expression of Cav2.3e mRNA in 20% (n=14/70) of DRG neurons, relative to Cav2.3a expression in 2.8% (n=2/70) of DRG neurons. Cav2.3e mRNA was mainly detected in small-sized neurons (n=12/14), but in only a few medium-sized neurons (n=2/14) and not in large-sized neurons, indicating the prominence of Cav2.3e in nociceptive DRG neurons. Moreover, Cav2.3e was preferentially expressed in tyrosine-kinase A (trkA)-positive, isolectin B4 (IB4)-negative and transient receptor potential vanilloid 1 (TRPV1)-positive neurons. These results suggest that Cav2.3e may be the main R-type Ca2+ channel isoform in nociceptive DRG neurons and thereby a potential target for pain treatment, not only in the trigeminal system but also in the spinal system.

Effects of Somatostatin on the Responses of Rostrally Projecting Spinal Dorsal Horn Neurons to Noxious Stimuli in Cats

Somatostatin (SOM) is a widely distributed peptide in the central nervous system and exerts a variety of hormonal and neural actions. Although SOM is assumed to play an important role in spinal nociceptive processing, its exact function remains unclear. In fact, earlier pharmacological studies have provided results that support either a facilitatory or inhibitory role for SOM in nociception. In the current study, the effects of SOM were investigated using anesthetized cats. Specifically, the responses of rostrally projecting spinal dorsal horn neurons (RPSDH neurons) to different kinds of noxious stimuli (i.e., heat, mechanical and cold stimuli) and to the A delta-and C-fiber activation of the sciatic nerve were studied. Iontophoretically applied SOM suppressed the responses of RPSDH neurons to noxious heat and mechanical stimuli as well as to C-fiber activation. Conversely, it enhanced these responses to noxious cold stimulus and A delta-fiber activation. In addition, SOM suppressed glutamate-evoked activities of RPSDH neurons. The effects of SOM were blocked by the SOM receptor antagonist cyclo-SOM. These findings suggest that SOM has a dual effect on the activities of RPSDH neurons; that is, facilitation and inhibition, depending on the modality of pain signaled through them and its action site.

Eugenol Inhibits ATP-induced P2X Currents in Trigeminal Ganglion Neurons

Eugenol is widely used in dentistry to relieve pain. We have recently demonstrated voltage-gated Na+ and Ca2+ channels as molecular targets for its analgesic effects, and hypothesized that eugenol acts on P2X3, another pain receptor expressed in trigeminal ganglion (TG), and tested the effects of eugenol by whole-cell patch clamp and Ca2+ imaging techniques. In the present study, we investigated whether eugenol would modulate 5'-triphosphate (ATP)-induced currents in rat TG neurons and P2X3-expressing human embryonic kidney (HEK) 293 cells. ATP-induced currents in TG neurons exhibited electrophysiological properties similar to those in HEK293 cells, and both ATP- and alpha,beta-meATP-induced currents in TG neurons were effectively blocked by TNP-ATP, suggesting that P2X3 mediates the majority of ATP-induced currents in TG neurons. Eugenol inhibited ATP-induced currents in both capsaicin-sensitive and capsaicin-insensitive TG neurons with similar extent, and most ATP-responsive neurons were IB4-positive. Eugenol inhibited not only Ca2+ transients evoked by alpha,beta-meATP, the selective P2X3 agonist, in capsaicin-insensitive TG neurons, but also ATP-induced currents in P2X3-expressing HEK293 cells without co-expression of transient receptor potential vanilloid 1 (TRPV1). We suggest, therefore, that eugenol inhibits P2X3 currents in a TRPV1-independent manner, which contributes to its analgesic effect.

Morphine-induced Modulation of Nociceptive Spinal Dorsal Horn Neuronal Activities after Formalin-induced Inflammatory Pain

In this study, we examined the morphine-induced modulation of the nociceptive spinal dorsal horn neuronal activities before and after formalin-induced inflammatory pain. Intradermal injection of formalin induced time-dependent changes in the spontaneous activity of nociceptive dorsal horn neurons. In naive cats before the injection of formalin, iontophoretically applied morphine attenuated the naturally and electrically evoked neuronal responses of dorsal horn neurons. However, neuronal responses after the formalin-induced inflammation were significantly increased by morphine. Bicuculline, GABAA antagonist, increased the naturally and electrically evoked neuronal responses of dorsal horn neurons. This increase in neuronal responses due to bicuculline after the formalin-induced inflammation was larger than that in the naive state, suggesting that basal GABAA tone increased after the formalin injection. Muscimol, GABAA agonist, reduced the neuronal responses before the treatment with formalin, but not after formalin treatment, again indicating an increase in the GABAergic basal tone after the formalin injection which saturated the neuronal responses to GABA agonist. Morphine-induced increase in the spinal nociceptive responses after formalin treatment was inhibited by co-application of muscimol. These data suggest that formalin-induced inflammation increases GABAA basal tone and the inhibition of this augmented GABAA basal tone by morphine results in a paradoxical morphine- induced increase in the spinal nociceptive neuronal responses after the formalin-induced inflammation.

Mechanism of Glutamate-inducedCa2+i Increase in Substantia Gelatinosa Neurons of Juvenile Rats

The glutamate receptors (GluRs) are key receptors for modulatory synaptic events in the central nervous system. It has been reported that glutamate increases the intracellularCa (2+) concentration ([Ca2+]i) and induces cytotoxicity. In the present study, we investigated whether the glutamate-induced[Ca2+]i increase was associated with the activation of ionotropic (iGluR) and metabotropic GluRs (mGluR) in substantia gelatinosa neurons, using spinal cord slice of juvenile rats (10~21 day) .[Ca2+]i was measured using conventional imaging techniques, which was combined with whole-cell patch clamp recording by incorporating fura-2 in the patch pipette. At physiological concentration of extracellularCa (2+), the inward current and[Ca2+]i increase were induced by membrane depolarization and application of glutamate. Dose-response relationship with glutamate was observed in bothCa (2+) signal and inward current. The glutamate-induced[Ca2+]i increase at holding potential of 70 mV was blocked by CNQX, an AMPA receptor blocker, but not by AP-5, a NMDA receptor blocker. The glutamate-induced[Ca2+]i increase inCa (2+) free condition was not affected by iGluR blockers. A selective mGluR (group I) agonist, RS-3, 5-dihydroxyphenylglycine (DHPG), induced[Ca2+]i increase at holding potential of 70 mV in SG neurons. These findings suggest that the glutamate-induced[Ca2+]i increase is associated with AMPA-sensitive iGluR and group I mGluR in SG neurons of rats.

The Effect of Nitric Oxide on Mechanical and Theraml Allodynia in Neuropathic Pain Model of Rat

BACKGROUND: Nitric oxide (NO) is known to play causative role in the development of neuropathic pain following peripheral nerve injury. However, it is yet to be investigated whether the role of NO differs in pain modalities, such as mechanical and thermal stimuli. Also, it has not been investigated whether NO has different roles in the stages of neuropathic pain - its development and maintenance. METHODS: Neuropathic pain was induced by a resection of the lumbar dorsal root 5, 6 (L 5, 6). After N-nitro-L-arginine methyl ester (L-NAME), an NO synthase inhibitor was injected intrathecally or locally around the dorsal root, we observed the behavioral response to the mechanical and thermal stimuli. RESULTS: Mechanical and thermal allodynia was inhibited by the application of L-NAME before the dorsal root injury. However, L-NAME did not affect the mechanical and thermal allodynia during the maintenance of neuropathic pain. CONCLUSIONS: We suggest that NO in the spinal cord or injured perineural site may play an important role in the induction of neuropathic pain, and may be associated with mechanical and thermal allodynia.

The Effects of GABA-receptor Antagonists on the Spinal Cord Stimulation-induced Antinociception in Cats / 대한마취과학회지

BACKGROUND: Spinal cord stimulation (SCS) is a clinical off spring of the gate-control theory and known as an effective treatment for pain from a neurogenic origin. The prolonged pain relief following a short stimulation period is believed to be related with the GABAergic system. The aims of this study were to see if the SCS, similar to that being used in clinical condition, suppressed the nociceptive transmission in the spinal dorsal horn, and if so, which type of GABA receptor may be involved in the antinociceptive process. METHODS: The cord dorsum potential (CDP) was recorded at the dorsal root entry zone of the lumbosacral enlargement for a long time period (60 min) in response to electrical stimulation of the dorsal root, respectively, after SCS in anesthetized cats. CDP was recorded after intrathecal application of bicuculline (GABA (A) receptor antagonist) and phaclofen (GABA (B) receptor antagonist) and 20 min after SCS that followed the intrathecal application of bicuculline or phaclofen. Asigma- and C-fiber wave responses were differentiated according to the conduction velocity. RESULTS: The C-fiber wave decreased significantly after SCS but the Asigma-fiber wave did not on the CDP. After intrathecal administration of bicuculline, the Asigma- and C-fiber waves increased significantly and bicuculline also prevented a SCS-induced reduction of the C-fiber wave. Phaclofen did not change the amplitude of Asigma- and C-fiber wave. When the phaclofen was administered intrathecally, SCS did not decrease the amplitude of the Asigma- and C-fiber waves. CONCLUSIONS: In conclusion, the present results indicate that SCS suppresses C-fiber transmission of acute nociceptive electrical stimuli and both GABA (A) and (B) receptors mediate the long-lasting antinociceptive effect of SCS.

Pathophysiology of Pain

Pain is a sensation induced by activation of the peripheral nociceptors when tissue is damaged by direct stimuli or has a possibility of damage. There exist nociceptors for detecting the noxious stimuli in periphery, and the nociceptive informations were transmitted via A delta- or C-fibers. Acute pain is caused by direct noxious stimuli, and chronic pains are produced by inflammation or nerve damage. The mechanisms of chronic pains are associated with the changes of cen-tral nervous system (CNS) as well as those in peripheral nocicpetors. Immune cells and neurotrophins are also involved in the mechanisms of chronic pain. Recently, there has been a tendency among pain researchers that chronic pain might be explained the plastic changes in the nociceptive synaptic transmission through the spinal cord. These are associated with changes in intracellular Ca(2+)concentration, subsequent intracellular signal transduction pathways, which result in changes in AMPA receptor dynamics. This sequential changes may induce allodynia and hyperalgesia observed in chronic pain patients. This review suggests new interpretation for pain mechanism and new approach for chronic pain.

DAMGO, a micro-opioid agonist and cholecystokinin-octapeptide have dual modulatory effects on capsaicin-activated current in rat dorsal root ganglion neurons

Capsaicin, a pungent ingredient of hot pepper, elicits an intense burning pain when applied cutaneously and intradermally. Activation of capsaicin-gated channel in. C-type dorsal root ganglion (DRG) neurons produces nonselective cationic currents. Although electrophysiological and biochemical properties of capsaicin-activated current (ICAP) were studied, the regulatory mechanism and intracellular signaling pathway are still unclear. In the present study, we investigated the modulations of ICAP by DAMGO (micro-opioid agonist) and cholecystokinin octapeptide (CCK-8). In 18 out of 86 cells, the amplitude of ICAP was significantly increased by DAMGO and completely reversed after washout, while ICAP was decreased by DAMGO in 25 cells. In 43 cells, DAMGO had no effect on ICAP. Mean action potential duration was significantly different between 'increased-by-DAMGO' group and 'decreased-by-DAMGO' group. Mean amplitudes of IH were not significantly different between both groups. CCK-8 reversibly enhanced the amplitude of ICAP (5/13). DAMGO also increased ICAP amplitude significantly in the same cells. The amplitude of ICAP was increased in additive manner by combined applications of DAMGO and CCK-8 in these cells. These results suggest that DAMGO and CCK-8 can either increase or decrease ICAP presumably depending on the subtypes of DRG cells and classified by electrophysiological properties.