AIMTo explore the cerebral cortex mechanism of visceral nociceptive sensation and its characteristics on the cell level, we investigated the membrane electrical properties of 176 stimulus-relative neurons of greater splanchnic nerve (GSN) in anterior cingulate gyrus (ACG) of 20 adult healthy cats.

METHODSWe used intracellular recording techniques of glass microelectrode and injected polarizing current into the neurons in ACG.

RESULTSAmong 176 neurons, 148 were visceral nociceptive neurons (VNNs) and 28 non-visceral nociceptive neurons (NVNNs). The membrane resistance (Rm), time constant (tau), membrane capacity (Cm), and the I-V curve of both VNNs and NVNNs in ACG were significantly different. The discharge frequency and amplitude of both VNNs and NVNNs produced by injecting depolarized current were different, too.

CONCLUSIONThe results suggest that structure of cell membrane, volume of the soma, and other aspects of morphology between VNNs and NVNNs in ACG may have significant differences. The results also might provide progressively experimental evidence for specific theory of pain sensation.

Animals ; Cats ; Gyrus Cinguli ; cytology ; physiology ; Membrane Potentials ; Nociceptors ; physiology ; Splanchnic Nerves ; physiology ; Visceral Afferents ; physiology

The physiological mechanism underlying the acupoint sensitization was evaluated systemically by using the method of electric physiology at spinal cord, medulla, and thalamus levels; the dynamic change of acupoint from the relative "silence" to the relative "activation" function was explained through the study on the dynamic process of acupoint sensitization; the biological process of the therapeutic effect of acupoint stimulation was illuminated through the research of the central mechanism underlining the dose effect relationship between the sensitive acupoint and the related brain area, thus scientific evidence for the functional link between the acupoint and internal organs as well as the nature of the acupoint were provided.
Acupuncture Points ; Acupuncture Therapy ; Animals ; Humans ; Moxibustion ; Nociceptors ; physiology ; Sensation ; Viscera ; innervation ; physiology ; Visceral Afferents ; physiology

AIMTo research the influence of noxious stimuli on the electric activities of pain-related neurons in several subnuclei of Amygdaloid Nucleus in rats.

METHODSTrains of the electric impulses applied to the sciatic nerve were used as noxious stimuli. The discharges of neurons were channeled off by glass microelectrode.

RESULTSPain-related neurons existed in several subnuclei of Amygdaloid Nucleus. When the noxious stimuli were administered the frequency of discharges of pain-excited neurons (PEN) was increased while the frequency of pain-inhibited neurons (PIN) was decreased to the lowest level. The electric activities of PEN and PIN were matched with each other. Intraperitoneal injection of morphine (10 mg/kg) antagonized the effects of noxious stimuli on the pain-related neurons.

CONCLUSIONSeveral subnuclei of Amygdaloid Nucleus play an essential role in perceiving, integrating and transmitting the pain impulses. They are a part of the central nervous system in which pain information is controlled and managed.

Amygdala ; physiology ; Animals ; Electrophysiology ; Neurons ; physiology ; Nociceptors ; physiology ; Rats ; Rats, Wistar

Using intracellular potential recording technique in vivo, a series of hyperpolarizing and depolarizing currents at different intensities with a 50-ms duration were injected to somatic nociceptive neurons (SNNs) and somatic non-nociceptive neurons (SNNNs) in the anterior cingulate gyrus (ACG) of cats. The membrane electrical responses of the neurons were recorded, and the membrane electrical parameters of the neurons were calculated for comparative study on membrane electrical properties of SNNs and SNNNs of the ACG. A total of 188 ACG neurons from 57 cats were recorded. Among the 188 neurons, 172 (91.5%) and 16 (8.5%) were SNNs and SNNNs, respectively. The I-V curves of SNNs and SNNNs in the ACG were "S" shapes. When the absolute value of injected current intensity was less than or equal to 1 nA (≤ 1 nA), the I and V of I-V curves of both SNNs and SNNNs were linearly correlated (rSNNs = 0.99, rSNNNs = 0.99). When the absolute value of injected current intensity was more than 1 nA, both SNNs and SNNNs showed a certain inward or outward rectification behavior. Compared with SNNNs, SNNs had stronger rectification and lower adaptability (P < 0.01). With the increase of injected current intensity, the changes of frequency of discharges of SNNs were higher than those of SNNNs. In addition, the membrane resistance (Rm), the membrane capacity (Cm) and the time constant (τ) of SNNs were larger than those of SNNNs (P < 0.05 or P < 0.01). The differences in the membrane electrical properties between SNNs and SNNNs in the ACG suggested the disparity in neuronal cell size and cell membrane structure between them. The results of this study provided the experimental basis for deeply elucidating the mechanisms of somatic nociceptive sensation and characteristics on the membrane electrical aspects of ACG neurons.
Animals ; Cats ; Gyrus Cinguli ; cytology ; Membrane Potentials ; Neurons ; physiology ; Nociceptors ; physiology

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*

Previous studies have indicated that the thalamic nucleus submedius (Sm) and the anterior pretectal nucleus (APtN) are involved in the descending modulation of nociception. The aim of the present study was to examine whether the opioid receptors in the Sm and APtN mediated the electroacupuncture (EA)-produced analgesia. The latency of tail flick (TF) reflex induced by radiant heat was used as an index of nociceptive response. The effects of microinjection of opioid receptor antagonist naloxone (1.0 microg, 0.5 ml) into Sm or APtN on the inhibition of the TF reflex induced by EA of "Zusanli" point (St. 36) with high- (5.0 mA) and low- (0.5 mA) intensity were examined in the lightly anesthetized rats. Sm microinjection of naloxone blocked the high- but not low-intensity EA-induced inhibition of the TF reflex. In contrast, naloxone applied to APtN blocked the low- but not high-intensity EA-induced inhibition. When naloxone applied to other brain regions adjacent to Sm or APtN, the EA-induced inhibition was not influenced under either high- or low-intensity condition. These results suggest that opioid receptors in Sm are involved in mediating the analgesia by high-intensity EA for exciting small (A-delta and C group) afferent fibers, while opioid receptors in APtN are involved in mediating the analgesia induced by low-intensity EA for only exciting large (A-beta) afferent fibers.
Acupuncture Analgesia ; Animals ; Electroacupuncture ; Naloxone ; pharmacology ; Narcotic Antagonists ; Nociceptors ; physiology ; Pain Measurement ; Rats ; Receptors, Opioid ; physiology ; Thalamic Nuclei ; physiology

The aim of the present study is to explore the role of anterior cingulate gyrus (ACG) in bilateral cerebral cortex in visceral nociceptive sensation. Electrical stimulation of greater splanchnic nerve (GSN) was used as visceral nociceptive stimulus, and intracellular recording techniques in vivo was used to record and analyze the responses to stimuli and spontaneous electric activities of the neurons in the bilateral ACG. According to the responses to electrical stimulation of GSN, the neurons in the bilateral ACG were divided into GSN-stimulus-relative neurons (GSRNs) and GSN-stimulus-irrelative ones. According to the characteristics of the evoked responses to electrical stimulation of the GSN, GSRNs could be further classified into visceral nociceptive neurons (VNNs) and non-visceral nociceptive neurons (NVNNs). VNNs included specific visceral nociceptive neurons (SVNNs) and non-specific visceral nociceptive neurons (NSVNNs). The results showed that the percentage of GSRNs in the contralateral ACG (38.18%) was significantly higher than that in the ipsilateral ACG (29.49%, P<0.01), suggesting although GSN afferent fibers project to bilateral ACG, they mainly project to the contralateral ACG. Compared with ipsilateral ACG, contralateral ACG possessed lower proportion of SVNNs and higher proportion of NSVNNs (P<0.01). The absolute values of resting potentials (RP) of GSRNs, VNNs, NVNNs and SVNNs in ipsilateral ACG were less than those of corresponding neurons in contralateral ACG. However, there were no significant differences in the absolute values of RP of NSVNNs between ipsilateral and contralateral ACG. There were no significant differences in modes, frequencies and amplitudes of spontaneous electric activities of VNNs and NVNNs between ipsilateral and contralateral ACG. Additionally, the percentage of neurons having spontaneous electric activities from VNNs was significantly higher than that from NVNNs, which indicated that the excitability of VNNs was higher than that of the NVNNs in bilateral ACG. These results suggest that the patterns and degrees of the responses to nociceptive GSN-stimulation of the ipsilateral and contralateral ACG are different, thus providing new experimental data for the asymmetry of functions of the bilateral brain.
Animals ; Cats ; Electric Stimulation ; Evoked Potentials ; physiology ; Female ; Gyrus Cinguli ; physiology ; Male ; Nociceptors ; physiology ; Viscera ; innervation ; Visceral Pain ; physiopathology

The neurotrophin and glial cell line-derived neurotrophic factor (GDNF) family of growth factors have been extensively studied because of their proven ability to regulate development of the peripheral nervous system. The neurotrophin family, which includes nerve growth factor (NGF), NT-3, NT4/5 and BDNF, is also known for its ability to regulate the function of adult sensory neurons. Until recently, little was known concerning the role of the GNDF-family (that includes GDNF, artemin, neurturin and persephin) in adult sensory neuron function. Here we describe recent data that indicates that the GDNF family can regulate sensory neuron function, that some of its members are elevated in inflammatory pain models and that application of these growth factors produces pain in vivo. Finally we discuss how these two families of growth factors may converge on a single membrane receptor, TRPV1, to produce long-lasting hyperalgesia.
Animals ; Glial Cell Line-Derived Neurotrophic Factors ; physiology ; Humans ; Hyperalgesia ; physiopathology ; Nerve Tissue Proteins ; physiology ; Neurturin ; physiology ; Nociceptors ; cytology ; TRPV Cation Channels ; physiology

The excitability of nociceptive neurons increases in the intact dorsal root ganglion (DRG) after a chronic compression, but the underlying mechanisms are still unclear. The aim of this study was to investigate the ionic mechanisms underlying the hyperexcitability of nociceptive neurons in the compressed ganglion. Chronic compression of DRG (CCD) was produced in adult rats by inserting two rods through the intervertebral foramina to compress the L4 DRG and the ipsilateral L5 DRG. After 5-7 d, DRG somata were dissociated and placed in culture for 12-18 h. In sharp electrode recording model, the lower current threshold and the depolarized membrane potential in the acutely dissociated CCD neurons were detected, indicating that hyperexcitability is intrinsic to the soma. Since voltage-gated K(+) (Kv) channels in the primary sensory neurons are important for the regulation of excitability, we hypothesized that CCD would alter K(+) current properties in the primary sensory neurons. We examined the effects of 4-aminopyridine (4-AP), a specific antagonist of A-type potassium channel, on the excitability of the control DRG neurons. With 4-AP in the external solution, the control DRG neurons depolarized (with discharges in some cells) and their current threshold decreased as the CCD neurons demonstrated, indicating the involvement of decreased A-type potassium current in the hyperexcitability of the injured neurons. Furthermore, the alteration of A-type potassium current in nociceptive neurons in the compressed ganglion was investigated with the whole-cell patch-clamp recording model. CCD significantly decreased A-type potassium current density in nociceptive DRG neurons. These data suggest that a reduction in A-type potassium current contributes, at least in part, to the increase in neuron excitability that may lead to the development of pain and hyperalgesia associated with CCD.
Animals ; Female ; Ganglia, Spinal ; physiopathology ; Hyperalgesia ; etiology ; physiopathology ; Neurons, Afferent ; physiology ; Nociceptors ; physiology ; Pain ; physiopathology ; Potassium Channels ; physiology ; Radiculopathy ; physiopathology ; Rats ; Rats, Sprague-Dawley

Spinal dorsal horn neurons play an important role in the processing of sensory information and are also targets of modulation by both endogenous and exogenous drugs. Propofol is an intravenous anesthetic and whether it has direct modulatory actions on sensory neuronal responses of the spinal cord dorsal horn has not been well studied. In the present study, a single dose (0.5 micromol) of propofol dissolved in dimethyl sulfoxide (DMSO) was directly applied onto the dorsal surface of the spinal cord and its effect was evaluated in 25 wide-dynamic-range (WDR) neurons and 10 low-threshold mechanoreceptive (LTM) neurons by using extracellular single unit recording technique in sodium pentobarbital anesthetized rats. Compared with the DMSO treatment, propofol produced a significant inhibition of WDR neuronal activity evoked by both noxious heat (45, 47, 49 or 53 degrees C, 15 s) and mechanical (pinch, 10 s) stimuli applied to their cutaneous receptive fields (cRF) on the ipsilateral hind paw skin. To investigate whether propofol exerts a modulatory effect on non-nociceptive afferent-mediated activity, the responses of WDR or LTM neurons to non-noxious brush and pressure were also evaluated. The non-noxious mechanically-evoked responses of both WDR and LTM neurons were significantly suppressed by propofol. The present results indicate that propofol has direct actions on the dorsal horn neurons of the spinal cord in rats. However, since both non-nociceptive and nociceptive afferent-mediated activity can be suppressed, the spinal effects of propofol are not likely to be specifically associated with anti-nociception.
Anesthetics, Intravenous ; Animals ; Dimethyl Sulfoxide ; Electrophysiology ; Male ; Mechanoreceptors ; drug effects ; Nociceptors ; physiology ; Posterior Horn Cells ; physiology ; Propofol ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Spinal Cord ; physiology