scholarly journals Activation of Lumbar Spinal Wide-Dynamic Range Neurons by a Sanshool Derivative

2009 ◽  
Vol 101 (4) ◽  
pp. 1742-1748 ◽  
Author(s):  
Carolyn M. Sawyer ◽  
Mirela Iodi Carstens ◽  
Christopher T. Simons ◽  
Jay Slack ◽  
T. Scott McCluskey ◽  
...  
Keyword(s):  
Time Course ◽  
Dynamic Range ◽  
Allyl Isothiocyanate ◽  
Intradermal Injection ◽  
Mustard Oil ◽  
Wide Dynamic Range ◽  
Low Threshold ◽  
Wdr Neurons ◽  
Almost All ◽  
Lumbar Spinal

The enigmatic sensation of tingle involves the activation of primary sensory neurons by hydroxy-α-sanshool, a tingly agent in Szechuan peppers, by inhibiting two-pore potassium channels. Central mechanisms mediating tingle sensation are unknown. We investigated whether a stable derivative of sanshool—isobutylalkenyl amide (IBA)—excites wide-dynamic range (WDR) spinal neurons that participate in transmission of chemesthetic information from the skin. In anesthetized rats, the majority of WDR and low-threshold units responded to intradermal injection of IBA in a dose-related manner over a >5-min time course and exhibited tachyphylaxis at higher concentrations (1 and 10%). Almost all WDR and low-threshold units additionally responded to the pungent agents mustard oil (allyl isothiocyanate) and/or capsaicin, prompting reclassification of the low-threshold cells as WDR. The results are discussed in terms of the functional role of WDR neurons in mediating tingle sensation.

Effects of TRPA1 Agonists Mustard Oil and Cinnamaldehyde on Lumbar Spinal Wide-Dynamic Range Neuronal Responses to Innocuous and Noxious Cutaneous Stimuli in Rats

2008 ◽  
Vol 99 (2) ◽  
pp. 415-425 ◽  
Author(s):  
Austin W. Merrill ◽  
Jason M. Cuellar ◽  
Justin H. Judd ◽  
Mirela Iodi Carstens ◽  
E. Carstens
Keyword(s):  
Dynamic Range ◽  
Allyl Isothiocyanate ◽  
Mustard Oil ◽  
Peripheral Sensitization ◽  
Mechanical Stimuli ◽  
Wide Dynamic Range ◽  
Noxious Heat ◽  
Before And After ◽  
Wdr Neurons ◽  
Lumbar Spinal

Mustard oil [allyl isothiocyanate (AITC)] and cinnamaldehyde (CA), agonists of the ion channel TRPA1 expressed in sensory neurons, elicit a burning sensation and heat hyperalgesia. We tested whether these phenomena are reflected in the responses of lumbar spinal wide-dynamic range (WDR) neurons recorded in pentobarbital-anesthetized rats. Responses to electrical and graded mechanical and noxious thermal stimulation were tested before and after cutaneous application of AITC or CA. Repetitive application of AITC initially increased the firing rate of 52% of units followed by rapid desensitization that persisted when AITC was reapplied 30 min later. Responses to noxious thermal, but not mechanical, stimuli were significantly enhanced irrespective of whether the neuron was directly activated by AITC. Windup elicited by percutaneous or sciatic nerve electrical stimulation was significantly reduced post-AITC. These results indicate that AITC produced central inhibition and peripheral sensitization of heat nociceptors. CA did not directly excite WDR neurons, and significantly enhanced responses to noxious heat while not affecting windup or responses to skin cooling or mechanical stimulation, indicating a peripheral sensitization of heat nociceptors.

Cutaneous responsiveness of lumbar spinal neurons in awake and halothane-anesthetized sheep

1995 ◽  
Vol 74 (4) ◽  
pp. 1549-1562 ◽  
Author(s):  
J. F. Herrero ◽  
P. M. Headley
Keyword(s):  
Dynamic Range ◽  
High Threshold ◽  
Relative Distribution ◽  
Control Mechanisms ◽  
Spinal Neurons ◽  
Halothane Anesthesia ◽  
Sensory Stimuli ◽  
Low Threshold ◽  
Wdr Neurons ◽  
Lumbar Spinal

1. To compare the responsiveness of lumbar spinal neurons to peripheral sensory stimuli under normal physiological conditions and under halothane anesthesia, we performed a study in sheep that were prepared chronically. This permitted recordings to be made in the same animals either when they were awake and free from recent surgery, drugs, and training and only partially restrained or when they were anesthetized with halothane. 2. We recorded 261 units in dorsal and ventral horns under conscious conditions. Of these, 19% had no detectable receptive field (RF) and 44% had responses dominated by proprioceptive inputs; these units were not investigated in detail. The remaining 96 neurons (37%) had clearly defined cutaneous RFs. Of these, most (72%) had wide-dynamic-range (WDR; convergent, multireceptive) properties, 19% were low-threshold mechanoreceptive (LTMR), and 9% were high-threshold mechanoreceptive (HTMR). These units with cutaneous RFs were investigated in greater detail. 3. The spontaneous activity under these awake conditions was low (< 4 spikes/s) for nearly all units in all three categories. The mechanical threshold of the most sensitive (central) part of the cutaneous RF was assessed with von Frey bristles. Thresholds were < 5 mN for all LTMR neurons, < 1-30 mN for WDR neurons, and > 80 mN for HTMR neurons. The size of the low-threshold cutaneous RFs was significantly larger for WDR neurons (mean 46 cm2) and HTMR neurons (45 cm2) than for LTMR neurons (24 cm2). The RFs were distributed all over the ipsilateral hindlimb. Large RFs were mostly proximal, whereas small RFs were distributed relatively evenly over the limb. 4. Recordings were made from a further 165 units while the animals were under halothane anesthesia. With 86 neurons having cutaneous peripheral RFs, the proportions having LTMR, HTMR, or WDR characteristics were very similar to those in awake animals. Under halothane the ongoing activity of WDR units was slightly (but significantly) less. The threshold to von Frey bristle stimulation was significantly higher only for WDR units, in both dorsal and ventral horns. The mean size of cutaneous RFs was significantly larger in all classes of units recorded under halothane anesthesia. For WDR units this was true for cells in both dorsal and ventral horns. This effect on mean values was due to a larger proportion of units with very large fields under anesthesia, particularly in the dorsal horn. 5. Comparison of the data from conscious animals with published results of acute experiments indicates that acute recording conditions do not distort the relative distribution and resting characteristics of these three functional categories of lumbar spinal neurons as much as might have been expected. 6. Halothane does not have major effects on the resting sensory responsiveness of spinal neurons with cutaneous RFs. The increase in RF area, which contrasts with most results from acute studies, is likely to be due to a dampening of descending inhibitory control mechanisms.

scholarly journals Facial injections of pruritogens or algogens elicit distinct behavior responses in rats and excite overlapping populations of primary sensory and trigeminal subnucleus caudalis neurons

2011 ◽  
Vol 106 (3) ◽  
pp. 1078-1088 ◽  
Author(s):  
Amanda Klein ◽  
Mirela Iodi Carstens ◽  
E. Carstens
Keyword(s):  
Dynamic Range ◽  
Allyl Isothiocyanate ◽  
Population Coding ◽  
Second Order ◽  
Mustard Oil ◽  
Sprague Dawley ◽  
Wide Dynamic Range ◽  
Sprague Dawley Rats ◽  
Dose Dependent ◽  
Trigeminal Subnucleus Caudalis

In the present study, we investigated whether intradermal cheek injection of pruritogens or algogens differentially elicits hindlimb scratches or forelimb wipes in Sprague-Dawley rats, as recently reported in mice. We also investigated responses of primary sensory trigeminal ganglion (TG) and dorsal root ganglion (DRG) cells, as well as second-order neurons in trigeminal subnucleus caudalis (Vc), to pruritic and algesic stimuli. 5-HT was the most effective chemical to elicit dose-dependent bouts of hindlimb scratches directed to the cheek, with significantly less forelimb wiping, consistent with itch. Chloroquine also elicited significant scratching but not wiping. Allyl isothiocyanate (AITC; mustard oil) elicited dose-dependent wiping with no significant scratching. Capsaicin elicited equivalent numbers of scratch bouts and wipes, suggesting a mixed itch and pain sensation. By calcium imaging, ∼6% of cultured TG and DRG cells responded to 5-HT. The majority of 5-HT-sensitive cells also responded to chloroquine, AITC, and/or capsaicin, and one-third responded to histamine. Using a chemical search strategy, we identified single units in Vc that responded to intradermal cheek injection of 5-HT. Most were wide dynamic range (WDR) or nociceptive specific (NS), and a few were mechanically insensitive. The large majority additionally responded to AITC and/or capsaicin and thus were not pruritogen selective. These results suggest that primary and second-order neurons responsive to pruritogens and algogens may utilize a population coding mechanism to distinguish between itch and pain, sensations that are behaviorally manifested by distinct hindlimb scratching and forelimb wiping responses.

Modulation of Trigeminal Spinal Subnucleus Caudalis Neuronal Activity Following Regeneration of Transected Inferior Alveolar Nerve in Rats

2008 ◽  
Vol 99 (5) ◽  
pp. 2251-2263 ◽  
Author(s):  
Kimiko Saito ◽  
Suzuro Hitomi ◽  
Ikuko Suzuki ◽  
Yuji Masuda ◽  
Junichi Kitagawa ◽  
...  
Keyword(s):  
Neuronal Activity ◽  
Dynamic Range ◽  
Inferior Alveolar Nerve ◽  
Evoked Responses ◽  
Wide Dynamic Range ◽  
Neuronal Mechanisms ◽  
The Face ◽  
Low Threshold ◽  
Wdr Neurons ◽  
Ganglion Neurons

Modulation of trigeminal spinal subnucleus caudalis neuronal activity following regeneration of transected inferior alveolar nerve in rats. To clarify the neuronal mechanisms of abnormal pain in the face innervated by the regenerated inferior alveolar nerve (IAN), nocifensive behavior, trigeminal ganglion neuronal labeling following Fluorogold (FG) injection into the mental skin, and trigeminal spinal subnucleus caudalis (Vc) neuronal properties were examined in rats with IAN transection. The mechanical escape threshold was significantly higher at 3 days and lower at 14 days after IAN transection, whereas head withdrawal latency to heat was significantly longer at 3, 14, and 60 days after IAN transection. The number of FG-labeled ganglion neurons was significantly reduced at 3 days after IAN transection but increased at 14 and 60 days. The number of wide dynamic range (WDR) neurons with background (BG) activity was significantly higher at 14 and 60 days after IAN transection compared with naïve rats, and the number of WDR and low-threshold mechanoreceptive (LTM) neurons with irregularly bursting BG activity was increased at these two time points. Mechanically evoked responses were significantly larger in WDR and LTM neurons 14 days after IAN transection compared with naïve rats. Heat- and cold-evoked responses in WDR neurons were significantly lower at 14 days after transection compared with naïve rats. Mechanoreceptive fields were also significantly larger in WDR and LTM neurons at 14 and 60 days after IAN transection. These findings suggest that these alterations may be involved in the development of mechanical allodynia in the cutaneous region innervated by the regenerated IAN.

Neurogenic hyperalgesia: central neural correlates in responses of spinothalamic tract neurons

1991 ◽  
Vol 66 (1) ◽  
pp. 228-246 ◽  
Author(s):  
D. A. Simone ◽  
L. S. Sorkin ◽  
U. Oh ◽  
J. M. Chung ◽  
C. Owens ◽  
...  
Keyword(s):  
Injection Site ◽  
Time Course ◽  
Dynamic Range ◽  
Intradermal Injection ◽  
High Threshold ◽  
Spinothalamic Tract ◽  
Burning Pain ◽  
Discharge Rates ◽  
Wdr Neurons ◽  
Magnitude Estimates

1. The contribution of activity in spinothalamic tract (STT) neurons to the pain and neurogenic hyperalgesia produced by an intradermal injection of 100 micrograms of capsaicin was investigated. Electrophysiological responses of identified STT neurons recorded in anesthetized monkeys were compared with psychophysical measurements of pain and hyperalgesia obtained in humans using identical stimuli. 2. Magnitude estimates of pain in humans were obtained after an injection of capsaicin or the vehicle. Capsaicin produced immediate burning pain that was most intense within 15 s after injection and then declined over the next 10–30 min. The vehicle produced no pain. 3. Cutaneous hyperalgesia to gentle stroking (allodynia) and also hyperalgesia to punctate stimulation developed in a wide area surrounding the capsaicin injection. Within this area, magnitude estimates of pain produced by a punctate stimulus (von Frey type with force of 225 mN) increased over preinjection values by an average of sixfold at test sites, 1, 2, and 3 cm away from the injection site. At the capsaicin injection site, magnitude estimates of pain in response to punctate simulation typically remained the same or were decreased. 4. After capsaicin, but not vehicle, the mean heat pain thresholds were lowered from approximately 45 degrees C before injection to 34 degrees C after, but only in the immediate vicinity of the injection site. At a site located 2 cm away, the thresholds were not significantly altered. Similarly, magnitude estimates of pain produced by suprathreshold heat stimuli were increased after capsaicin only at the injection site. 5. STT neurons were classified as high-threshold (HT) or wide-dynamic-range (WDR) cells according to responses evoked by graded cutaneous mechanical stimulation. An intradermal injection of capsaicin excited 4 of 7 HT cells and 10 of 12 WDR cells. The discharge rates of STT neurons correlated in time course with the magnitude estimates of pain in humans. The correlation was considerably better for WDR than for HT neurons, suggesting a predominant contribution of WDR neurons to the pain from capsaicin. 6. Capsaicin significantly increased the responses of HT neurons (9-fold) and the responses of WDR neurons (2-fold) to stroking the skin within the receptive field. Similar increases in responses to a standard punctate stimulus were observed at test sites, 1, 2, and 3 cm away from the injection site. After injection of vehicle, the responses to punctate stimulation increased by a mean of only 1.2- and 1.4-fold for HT and WDR neurons, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)

Activation of Spinal Wide Dynamic Range Neurons by Intracutaneous Microinjection of Nicotine

1999 ◽  
Vol 82 (6) ◽  
pp. 3046-3055 ◽  
Author(s):  
Steven L. Jinks ◽  
E. Carstens
Keyword(s):  
Nicotinic Acetylcholine Receptors ◽  
Acetylcholine Receptors ◽  
Dynamic Range ◽  
Receptive Fields ◽  
Threshold Region ◽  
Partial Recovery ◽  
Evoked Responses ◽  
Wide Dynamic Range ◽  
Analgesic Effects ◽  
Wdr Neurons

Nicotine evokes pain in the skin and oral mucosa and excites a subpopulation of cutaneous nociceptors, but little is known about the central transmission of chemogenic pain. We have investigated the responses of lumbar spinal wide dynamic range (WDR)-type dorsal horn neurons to intracutaneous (ic) microinjection of nicotine in pentobarbital-anesthetized rats. Nearly all (97%) units responded to nicotine microinjected ic (1 μl) into the low-threshold region of the hind-paw mechanosensitive receptive field in a concentration-related manner (0.01–10%). Responses to repeated injections of 10% nicotine exhibited tachyphylaxis at 5-, 10-, and 15-min interstimulus intervals. Significant tachyphylaxis was not seen with 1% nicotine. All nicotine-responsive units tested ( n = 30) also responded to ic histamine (1 μl, 3%) and did not exhibit tachyphylaxis to repeated histamine. However, there was significant cross-tachyphylaxis of nicotine to histamine. Thus 5 min after ic nicotine, histamine-evoked responses were attenuated significantly compared with the initial histamine-evoked response prior to nicotine, with partial recovery over the ensuing 15 min. Neuronal excitation by ic nicotine was not mediated by histamine H1 receptors because ic injection of the H1 receptor antagonist, cetirizine, had no effect on ic nicotine-evoked responses, whereas it significantly attenuated ic histamine-evoked responses in the same neurons. The lowest-threshold portion of cutaneous receptive fields showed a significant expansion in area at 20 min after ic nicotine 10%, indicative of sensitization. Responses to 1% nicotine were significantly reduced after ic injection of the nicotinic antagonist, mecamylamine (0.1% ic), with no recovery over the ensuing 40–60 min. These data indicate that nicotine ic excites spinal WDR neurons, partly via neuronal nicotinic acetylcholine receptors that are presumably expressed in cutaneous nociceptor terminals. Repeated injections of high concentrations of nicotine led to tachyphylaxis and cross-tachyphylaxis with histamine, possibly relevant to peripheral analgesic effects of nicotine.

Effects of tooth pulp deafferentation on nociceptive and nonnociceptive neurons of the feline trigeminal subnucleus caudalis (medullary dorsal horn)

1989 ◽  
Vol 61 (6) ◽  
pp. 1197-1206 ◽  
Author(s):  
J. W. Hu ◽  
B. J. Sessle
Keyword(s):  
Dynamic Range ◽  
Tooth Pulp ◽  
Medullary Dorsal Horn ◽  
Somatosensory Neurons ◽  
Low Threshold ◽  
Adult Cats ◽  
Mandibular Teeth ◽  
Wdr Neurons ◽  
Induced Changes ◽  
And Control

1. Effects of deafferentation of the tooth pulps of the posterior mandibular teeth were studied in single neurons recorded in the ipsilateral subnucleus caudalis of the trigeminal (V) spinal tract nucleus of adult cats and kittens. The functional properties of neurons in each anesthetized animal were determined electro-physiologically in a series of microelectrode penetrations of the subnucleus. 2. The more than 800 neurons investigated could be subdivided on the basis of their cutaneous mechanoreceptive field properties into low-threshold mechanoreceptive (LTM) neurons, wide dynamic range (WDR) neurons, or nociceptive-specific (NS) neurons. Comparisons of neuronal properties were made between control (intact) cats and 7-15 day deafferented cats studied in a blind design, as well as groups of longer term deafferented cats, and kittens undergoing a “natural” deafferentation as a result of exfoliation of primary teeth. 3. There was no apparent change in the somatotopic pattern of organization of the subnucleus in the kittens and pulp-deafferented cats and no statistically significant differences were noted between kittens and control cats in any property except for alterations in the incidence of spontaneously active neurons. 4. Limited but statistically significant alterations were noted in some of the neuronal properties in the deafferented cats. These changes were especially apparent in the LTM neurons. The incidence of spontaneous activity was significantly decreased in the neurons of most long-term deafferented groups of cats. In the 7–15 day deafferented group, significantly more LTM neurons had a mechanoreceptive field involving all three divisions of the V nerve, and there was a significant increase in the incidence of LTM neurons activated by electrical stimulation of intraoral sites. Mechanosensitive neurons responsive only to tap stimuli were found only in the deafferented groups of cats. 5. These alterations in caudalis contrast with previous reports claiming marked hyperexcitability of caudal V brain stem neurons as a consequence of deafferentation and implicating such effects in the development of pain. However, some of the changes are in general not inconsistent with deafferentation-induced changes reported in spinal somatosensory neurons and with the pulp deafferentation-induced changes that we have recently documented in LTM neurons of subnucleus oralis of the V spinal tract nucleus of adult cats.(ABSTRACT TRUNCATED AT 400 WORDS)

Halothane Suppression of Spinal Sensory Neuronal Responses to Noxious Peripheral Stimuli Is Mediated, in Part, by Both GABAAand Glycine Receptor Systems

2002 ◽  
Vol 97 (2) ◽  
pp. 412-417 ◽  
Author(s):  
Masanori Yamauchi ◽  
Hiroshi Sekiyama ◽  
Steven G. Shimada ◽  
J. G. Collins
Keyword(s):  
Dynamic Range ◽  
Glycine Receptor ◽  
Gamma Aminobutyric Acid ◽  
Neuronal Responses ◽  
General Anesthetic ◽  
Gaba A ◽  
Low Threshold ◽  
Noxious Stimuli ◽  
Evoked Activity ◽  
Wdr Neurons

Background A major effect of general anesthesia is lack of response in the presence of a noxious stimulus. Anesthetic depression of spinal sensory neuronal responses to noxious stimuli is likely to contribute to that essential general anesthetic action. The authors tested the hypothesis that gamma-aminobutyric acid receptor type A (GABA(A)) and strychnine-sensitive glycine receptor systems mediate halothane depression of spinal sensory neuronal responses to noxious stimuli. Methods Extracellular activity of single spinal dorsal horn wide dynamic range (WDR) neurons was recorded in decerebrate, spinal cord transected rats. Neuronal responses to noxious (thermal and mechanical) and nonnoxious stimuli were examined in the drug-free state. Subsequently, cumulative doses (0.1-2.0 mg/kg) of bicuculline (GABA(A) antagonist) or strychnine (glycine antagonist) were administered intravenously in the absence or presence of 1 minimum alveolar concentration (MAC) of halothane. Results Halothane, 1.1%, depressed the response of WDR neurons to both forms of noxious stimuli. Antagonists, by themselves, had no effect on noxiously evoked activity. However, bicuculline and strychnine (maximum cumulative dose, 2.0 mg/kg) partially but significantly reversed the halothane depression of noxiously evoked activity. Similar results were seen with most, but not all, forms of nonnoxiously evoked activity. In the absence of halothane, strychnine significantly increased neuronal responses to low threshold receptive field brushing. Conclusion Halothane depression of spinal WDR neuronal responses to noxious and most nonnoxious stimuli is mediated, in part, by GABA(A) and strychnine-sensitive glycine systems. A spinal source of glycine tonically inhibits some forms of low threshold input to WDR neurons.

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