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.

Transient spinal cord ischemia induces temporary hypersensitivity of dorsal horn wide dynamic range neurons to myelinated, but not unmyelinated, fiber input

1992 ◽  
Vol 68 (2) ◽  
pp. 384-391 ◽  
Author(s):  
J. X. Hao ◽  
X. J. Xu ◽  
Y. X. Yu ◽  
A. Seiger ◽  
Z. Wiesenfeld-Hallin
Keyword(s):  
Spinal Cord ◽  
Dorsal Horn ◽  
Mechanical Stimulation ◽  
Dynamic Range ◽  
Background Activity ◽  
Spinal Cord Ischemia ◽  
Receptive Fields ◽  
Wide Dynamic Range ◽  
C Fiber ◽  
Wdr Neurons

1. The activity of 197 single dorsal horn neurons was recorded extracellularly in the spinal cord of decerebrate, spinalized, unanesthetized rats. The response properties of 174 wide dynamic range (WDR) neurons to electrical, mechanical, and thermal stimulation in three groups of rats were studied:normal, 1-4 days after transient spinal cord ischemia induced photochemically by laser irradiation when the rats exhibited behavioral hypersensitivity to mechanical stimuli (allodynia), and 10-20 days after spinal ischemia when the allodynia had ceased. 2. In normal rats, the responses of dorsal horn WDR neurons to suprathreshold electrical stimulation of their receptive fields consisted of a short-latency (A) and a long-latency (C) response. In 77% of the neurons (57/74), there was a separation between the A- and C-fiber responses. The response threshold (defined as 20% increase in neuronal discharges above background activity) to mechanical stimulation applied with calibrated von Frey hairs was 13.8 g, and the discharges of these neurons to graded stimulation increased linearly. 3. In 68% of WDR neurons in allodynic rats (38/56), the response to suprathreshold electrical stimuli was a single burst with no separation between A- and C-fiber responses. The magnitude and duration of the response were significantly increased compared with those recorded in normal rats. The sensitivity of these neurons to mechanical stimulation was also greatly increased, expressed by a lowered threshold (2.1 +/- 0.3 g, mean +/- SE) and a shift to the left of the nonlinear stimulus-response curve. The background activity of the neurons and the size of the receptive fields were, however, unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

scholarly journals Manipulating midbrain dopamine neurons and reward-related behaviors with light-controllable nicotinic acetylcholine receptors

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Romain Durand-de Cuttoli ◽  
Sarah Mondoloni ◽  
Fabio Marti ◽  
Damien Lemoine ◽  
Claire Nguyen ◽  
...  
Keyword(s):  
Nicotinic Acetylcholine Receptors ◽  
Acetylcholine Receptors ◽  
Direct Evidence ◽  
Dynamic Range ◽  
Dopamine Neurons ◽  
Optical Manipulation ◽  
Chemical Genetic ◽  
Brain Circuits ◽  
Midbrain Dopamine ◽  
Firing Properties

Dopamine (DA) neurons of the ventral tegmental area (VTA) integrate cholinergic inputs to regulate key functions such as motivation and goal-directed behaviors. Yet the temporal dynamic range and mechanism of action of acetylcholine (ACh) on the modulation of VTA circuits and reward-related behaviors are not known. Here, we used a chemical-genetic approach for rapid and precise optical manipulation of nicotinic neurotransmission in VTA neurons in living mice. We provide direct evidence that the ACh tone fine-tunes the firing properties of VTA DA neurons through β2-containing (β2*) nicotinic ACh receptors (nAChRs). Furthermore, locally photo-antagonizing these receptors in the VTA was sufficient to reversibly switch nicotine reinforcement on and off. By enabling control of nicotinic transmission in targeted brain circuits, this technology will help unravel the various physiological functions of nAChRs and may assist in the design of novel therapies relevant to neuropsychiatric disorders.

Alteration of Medullary Dorsal Horn Neuronal Activity Following Inferior Alveolar Nerve Transection in Rats

2001 ◽  
Vol 86 (6) ◽  
pp. 2868-2877 ◽  
Author(s):  
Koichi Iwata ◽  
Takao Imai ◽  
Yoshiyuki Tsuboi ◽  
Akimasa Tashiro ◽  
Akiko Ogawa ◽  
...  
Keyword(s):  
Dorsal Horn ◽  
Neuronal Activity ◽  
Dynamic Range ◽  
Escape Behavior ◽  
Receptive Fields ◽  
Inferior Alveolar Nerve ◽  
Skin Incision ◽  
Medullary Dorsal Horn ◽  
Whisker Pad ◽  
Wdr Neurons

The effects of inferior alveolar nerve (IAN) transection on escape behavior and MDH neuronal activity to noxious and nonnoxious stimulation of the face were precisely analyzed. Relative thresholds for escape from mechanical stimulation applied to the whisker pad area ipsilateral to the transection were significantly lower than that for the contralateral and sham-operated whisker pad until 28 days after the transection, then returned to the preoperative level at 40 days after transection. A total of 540 neurons were recorded from the medullary dorsal horn (MDH) of the nontreated naive rats [low-threshold mechanoreceptive (LTM), 27; wide dynamic range (WDR), 31; nociceptive specific (NS), 11] and sham-operated rats with skin incision (LTM, 34; WDR, 30; NS, 23) and from the ipsilateral (LTM, 82; WDR, 82; NS, 31) and contralateral MDH relative to the IAN transection (LTM, 77; WDR, 82; NS, 33). The electrophysiological properties of these neurons were precisely analyzed. Background activity of WDR neurons on the ipsilateral side relative to the transection was significantly increased at 2–14 days after the operation as compared with that of naive rats. Innocuous and noxious mechanical-evoked responses of LTM and WDR neurons were significantly enhanced at 2–14 days after IAN transection. The mean area of the receptive fields of WDR neurons was significantly larger on the ipsilateral MDH at 2–7 days after transection than that of naive rats. We could not observe any modulation of thermal responses of WDR and NS neurons following IAN transection. Also, no MDH neurons were significantly affected in the rats with sham operations. The present findings suggest that the increment of neuronal activity of WDR neurons in the MDH following IAN transection may play an important role in the development of the mechano-allodynia induced in the area adjacent to the area innervated by the injured nerve.

α2-Adrenoceptors Modulate NMDA-Evoked Responses of Neurons in Superficial and Deeper Dorsal Horn of the Medulla

1998 ◽  
Vol 80 (4) ◽  
pp. 2210-2214 ◽  
Author(s):  
Kai-Ming Zhang ◽  
Xiao-Min Wang ◽  
Angela M. Peterson ◽  
Wen-Yan Chen ◽  
Sukhbir S. Mokha
Keyword(s):  
Dorsal Horn ◽  
Dynamic Range ◽  
Inhibitory Effect ◽  
Male Rats ◽  
Evoked Responses ◽  
Superficial Dorsal Horn ◽  
Nociceptive Neurons ◽  
Adrenoceptor Antagonist ◽  
Medullary Dorsal Horn ◽  
Wdr Neurons

Kai-Ming Zhang, Xiao-Min Wang, Angela M. Peterson, Wen-Yan Chen, and Sukhbir S. Mokha. α2-Adrenoceptors modulate NMDA-evoked responses of neurons in the superficial and deeper dorsal horn of the medulla. J. Neurophysiol. 80: 2210–2214, 1998. Extracellular single unit recordings were made from neurons in the superficial and deeper dorsal horn of the medulla (trigeminal nucleus caudalis) in 21 male rats anesthetized with urethan. NMDA produced an antagonist-reversible excitation of 46 nociceptive as well as nonnociceptive neurons. Microiontophoretic application of a preferential α2-adrenoceptor (α2AR) agonist, (2-[2,6-dichloroaniline]-2-imidazoline) hydrochloride (clonidine), reduced the NMDA-evoked responses of 86% (6/7) of nociceptive-specific (NS) neurons, 82% (9/11) of wide dynamic range (WDR) neurons, and 67% (4/6) of low-threshold (LT) neurons in the superficial dorsal horn. In the deeper dorsal horn, clonidine inhibited the NMDA-evoked responses of 94% (16/17) of NS and WDR neurons and 60% (3/5) of LT neurons. Clonidine facilitated the NMDA-evoked responses in 14% (1/17) of NS, 9% (1/11) of WDR, and 33% (2/6) of LT neurons in the superficial dorsal horn. Idazoxan, an α2AR antagonist, reversed the inhibitory effect of clonidine in 90% (9/10) of neurons, whereas prazosin, an α1-adrenoceptor antagonist with affinity for α2BAR, and α2CAR, were ineffective. We suggest that activation of α2ARs produces a predominantly inhibitory modulation of the NMDA-evoked responses of nociceptive neurons in the medullary dorsal horn.

Changes in tonic descending inhibition of spinal neurons with articular input during the development of acute arthritis in the cat

1991 ◽  
Vol 66 (3) ◽  
pp. 1021-1032 ◽  
Author(s):  
H. G. Schaible ◽  
V. Neugebauer ◽  
F. Cervero ◽  
R. F. Schmidt
Keyword(s):  
Acute Inflammation ◽  
Dynamic Range ◽  
Receptive Fields ◽  
Response Threshold ◽  
Mechanical Stimuli ◽  
Spinal Neurons ◽  
Descending Inhibition ◽  
Intact State ◽  
Wdr Neurons ◽  
Alpha Chloralose

1. In 15 alpha-chloralose-anesthetized cats we studied the presence of tonic descending inhibition (TDI) of spinal neurons with input from the knee and its modulation during an acute inflammation of this joint. TDI of spinal neurons with articular input was assessed by applying reversible cold blocks to the lower thoracic cord. The amount of descending inhibition was estimated from the induction and/or increase of resting discharges and of the responses to mechanical stimuli to the knee and other structures during the transitory and reversible blocks. In each experiment one or a few neurons were investigated while the joint was in normal condition [altogether 15 nociceptive-specific (NS) and 6 wide-dynamic-range (WDR) neurons]. One of the neurons was then selected for long-term recordings during which an acute inflammation in the knee was induced by the intra-articular injection of kaolin and carrageenan. Before and during developing arthritis, cold blocks were applied to examine whether the amount of TDI would change during the inflammatory process. 2. The neurons with input from the normal knee were under TDI because application of the cold block induced or increased resting discharges and the responses to noxious compression of the knee and the adjacent thigh and lower leg. In 10 of 15 NS neurons, the response threshold was lowered into the innocuous range. In 9 of 17 cells tested, the excitatory receptive field expanded to the ipsilateral paw, and 4 neurons became inhibited by paw compression. Seven of 18 neurons tested revealed inhibitory receptive fields on the contralateral leg during cold block. The neurons were located in laminae IV-VII. 3. Fourteen neurons were continuously monitored during development of inflammation, and changes in the effectiveness of TDI were assessed by blocking the cord before and during the development of arthritis. In most neurons baseline resting activity in the intact state of the cord increased while the arthritis developed. This inflammation-evoked enhancement of resting discharges was more pronounced during periods of spinalization. Consequently, the differences between the resting discharges in the cold-blocked and the intact state were progressively enhanced in arthritis. 4. After induction of arthritis, the responses to compression of the knee joint increased in the intact state as well as during cold blocks. In 11 of 14 neurons, the differences between the responses in the spinal and intact state were progressively enlarged during the development of inflammation. A similar result was obtained for flexion of the injected knee.(ABSTRACT TRUNCATED AT 400 WORDS)

Changes in Response Properties and Receptive Fields of Spinal Dorsal Horn Neurons in Rats after Surgical Incision in Hairy Skin

2005 ◽  
Vol 102 (1) ◽  
pp. 141-151 ◽  
Author(s):  
Mikito Kawamata ◽  
Masayuki Koshizaki ◽  
Steven G. Shimada ◽  
Eichi Narimatsu ◽  
Yuji Kozuka ◽  
...  
Keyword(s):  
Dynamic Range ◽  
Receptive Fields ◽  
Gamma Aminobutyric Acid ◽  
Wide Dynamic Range ◽  
Surgical Incision ◽  
Dorsal Horn Neurons ◽  
Hairy Skin ◽  
Noxious Stimuli ◽  
Made In ◽  
Wide Dynamic Range Neurons

Background Mechanical hyperalgesia and allodynia associated with chemical irritant application are mediated by spinal high-threshold (HT) as well as wide-dynamic-range neurons as a result of "central sensitization." Because the pathophysiology of pain is thought to differ depending on the type of injury and may vary between hairy and glabrous skin, the authors examined changes in properties of spinal dorsal horn neurons after surgical incisions in hairy skin of rats to obtain insights into the mechanisms of postoperative pain. Methods Withdrawal responses to punctate mechanical stimulation and gentle brushing were measured in awake rats in an area adjacent to the injured site (primary area) and in an area 2 cm from the injured site (secondary area) after 1-cm longitudinal incisions through the hairy skin, fascia, and muscle had been made in the hindquarters. In a separate study, responses of spinal wide-dynamic-range, HT, and low-threshold neurons to nonnoxious and noxious stimuli were recorded before and after similar incisions had been made in the centers of their receptive fields. Effects of spinal application of the gamma-aminobutyric acid A receptor antagonist bicuculline (15 microg) on responses of HT neurons were then studied. Results Awake rats showed primary and secondary hyperalgesia to punctate mechanical stimulation 30 min after the incision and thereafter for 4 days and 1 day, respectively. Mechanical allodynia associated with brush stimulation was only seen in the primary area 30 min after the incision and thereafter for 1 day. The incision resulted in increases in activity of wide-dynamic-range neurons (receptive field sizes and responses to both innocuous and noxious stimuli). HT neurons did not respond to innocuous stimulation and showed very small increases or no changes in receptive field size and responses to noxious stimuli after the incision. However, the majority of HT neurons began to respond to innocuous stimuli after application of bicuculline (15 microg/50 microl) to the spinal cord. Conclusions The results suggest that wide-dynamic-range neurons are responsible for behavioral hyperexcitability after surgical incision but that HT neurons are not involved in the hyperexcitability, despite the fact that HT neurons are capable of responding to innocuous stimuli by reversal of gamma-aminobutyric acid-mediated inhibition.

Responses of primate spinothalamic neurons to graded and to repeated noxious heat stimuli

1979 ◽  
Vol 42 (5) ◽  
pp. 1370-1389 ◽  
Author(s):  
D. R. Kenshalo ◽  
R. B. Leonard ◽  
J. M. Chung ◽  
W. D. Willis
Keyword(s):  
Skin Temperature ◽  
Power Function ◽  
Dynamic Range ◽  
Background Activity ◽  
Receptive Fields ◽  
Peak Frequency ◽  
High Threshold ◽  
Wide Dynamic Range ◽  
Noxious Heat ◽  
Thermal Stimuli

1. The responses of primate spinothalamic tract cells innervating the glabrous skin of the foot to noxious thermal stimuli have been examined. 2. Of the 41 cells studied, 98% responded to noxious thermal stimuli. Heating the cutaneous receptive field with a series of stimuli from 35 to 43, 47, and 50 degrees C produced a graded increase in discharge rate. The responses were characterized by an onset, which occurred after the temperature change had either slowed or stopped, an acceleration in the discharge up to a peak, and then an adaptation to a new base-line level. The time constants of adaptation were faster than those reported for C polymodal nociceptors. 3. No systematic differences were found in the responses to noxious thermal stimuli of cells with wide dynamic range receptive fields and of cells with narrow dynamic range, high-threshold receptive fields. There were also no differences in the responses of cells located in the marginal zone and of cells located in the neck of the dorsal horn. 4. The relationship between peak frequency and final skin temperature with a 30 s stimulus duration can best be described by a power function with an exponent of 2.1. An increase in the stimulus duration to 120 s resulted in an increase in the exponent of the power function to 3.2. 5. Repetition of the series of 30-s heat stimuli resulted in an increase in peak frequency, total impulse count, and background activity. Repetition of stimuli having a duration of 120 s produced an increase in the peak frequency at 43 and 45 degrees C, a smaller increase at 47 degrees C, and a decrease at 50 degrees C. Background activity was increased by the lower temperature stimuli, but was decreased following higher temperature stimuli. 6. In six additional cells, the skin was heated with three consecutive presentations at each temperature level (43, 45, 47, and 50 degrees C) for 30 s. No change was observed in the peak frequencies of the responses to successive stimuli of the same intensity. However, the exponent of the power function relating the average peak frequency for the six cells to changes in skin temperature was 3.9. This exponent was larger than that seen when two series of graded heat stimuli of 120 s duration were used, indicating more sensitization despite the fact the total time of exposure to noxious heat was less. 7. A role for both high-threshold and wide dynamic range spinothalamic cells in transmitting nociceptive information to the diencephalon is postulated.

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