Stimulus Response Functions

2008 ◽  
Vol 294 (4) ◽  
pp. G963-G970 ◽  
Author(s):  
Amanda J. Page ◽  
Tracey A. O'Donnell ◽  
L. Ashley Blackshaw

Despite universal use of opioids in the clinic to inhibit pain, there is relatively little known of their peripheral actions on sensory nerve endings, where in fact they may be better targeted with more widespread applications. Here we show differential effects of μ-, κ-, and δ-opioids on mechanosensitive ferret esophageal vagal afferent endings investigated in vitro. The effects of selective agonists [d-Ala2,N-Me-Phe4,Gly-ol5]-enkephalin (DAMGO), 2-(3, 4-dichlorophenyl)- N-methyl- N-[(1S)-1phenyl-2-(1-pyrrolidinyl) ethyl] acetamide hydrochlorine (ICI 199441), and (+)-4-[(αR)-α-((2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl]- N, N-diethylbenzamide (SNC-80), respectively, on mechanosensory stimulus-response functions were quantified. DAMGO (10−7 to 10−5 M) reduced the responses of tension receptors to circumferential tension (1–5 g) by up to 50%, and the responses of mucosal receptors to mucosal stroking (10–1,000 mg von Frey hair) by >50%. DAMGO effects were reversed by naloxone (10−5 M). Tension/mucosal (TM) receptor responses to tension and stroking were unaffected by DAMGO. ICI 199441 (10−6 to 10−5 M) potently inhibited all responses except TM receptor responses to tension, and SNC-80 (10−5 to 10−3 M) had no effect other than a minor inhibition of mucosal receptor responses to intense stimuli at 10−3 M. We conclude that μ- and κ-opioids have potent and selective peripheral effects on esophageal vagal afferents that may have applications in treatment of disorders of visceral sensation.


2008 ◽  
Vol 100 (5) ◽  
pp. 2771-2783 ◽  
Author(s):  
Nevena Milenkovic ◽  
Christiane Wetzel ◽  
Rabih Moshourab ◽  
Gary R. Lewin

Here we have systematically characterized the stimulus response properties of mechanosensitive sensory fibers in the mouse saphenous nerve. We tested mechanoreceptors and nociceptors with defined displacement stimuli of varying amplitude and velocity. For each sensory afferent investigated we measured the mechanical latency, which is the delay between the onset of a ramp displacement and the first evoked spike, corrected for conduction delay. Mechanical latency plotted as a function of stimulus strength was very characteristic for each receptor type and was very short for rapidly adapting mechanoreceptors (<11 ms) but very long in myelinated and unmyelinated nociceptors (49–114 ms). Increasing the stimulus speed decreased mechanical latency in all receptor types with the notable exception of C-fiber nociceptors, in which mean mechanical latency was not reduced ≲100 ms, even with very fast ramp stimuli (2,945 μm/s). We examined stimulus response functions and mechanical latency at two different temperatures (24 and 32°C) and found that stimulus response properties of almost all mechanoreceptors were not altered in this range. A notable exception to this rule was found for C-fibers in which mechanical latency was substantially increased and stimulus response functions decreased at lower temperatures. We calculated Q10 values for mechanical latency in C-fibers to be 5.1; in contrast, the Q10 value for conduction velocity for the same fibers was 1.4. Finally, we examined the effects of short-term inflammation (2–6 h) induced by carrageenan on nociceptor and mechanoreceptor sensitivity. We did not detect robust changes in mechanical latency or stimulus response functions after inflammation that might have reflected mechanical sensitization under the conditions tested.


2000 ◽  
Vol 83 (4) ◽  
pp. 2179-2191 ◽  
Author(s):  
R. M. Slugg ◽  
R. A. Meyer ◽  
J. N. Campbell

The goal of this study was to determine the capacity of primary afferent nociceptive fibers (nociceptors) to encode information about noxious mechanical stimuli in primates. Teased-fiber techniques were used to record from 14 A-fiber nociceptors and 18 C-fiber nociceptors that innervated the hairy skin. Stimulus-response functions were examined with an ascending series of force-controlled stimuli. Stimulus-interaction effects were examined with use of a series of paired stimuli in which the interval between the stimulus pairs was varied systematically. Both A-fiber and C-fiber nociceptors exhibited a slowly adapting response to the stepped force stimuli. The response of the A fibers increased monotonically with increasing force, whereas the response of the C fibers reached a plateau at low force levels. The slope of the stimulus-response function for the A fibers was significantly steeper than that for the C fibers, and the total response was greater. The A fibers also provided more discriminative information regarding stimulus intensity. The C fibers demonstrated a significant fatigue in response when the interstimulus interval between the paired stimuli was ≤150 s, whereas the A fibers did not demonstrate a significant fatigue until the interstimulus interval was ≤30 s. This fatigue in response was not due to changes in tissue compliance. These results suggest that A- and C-fiber nociceptors have different mechanical transduction mechanisms. A-fiber nociceptors exhibit steeper stimulus-response functions and less fatigue than C-fiber nociceptors.


2002 ◽  
Vol 87 (1) ◽  
pp. 103-112 ◽  
Author(s):  
Volker Neugebauer ◽  
Weidong Li

Pain has a strong emotional dimension, and the amygdala plays a key role in emotionality. The processing of nociceptive mechanical and thermal information was studied in individual neurons of the central nucleus of the amygdala, the target of the spino-parabrachio-amygdaloid pain pathway and a major output nucleus of the amygdala. This study is the first to characterize nociceptive amygdala neurons with input from deep tissue, particularly the knee joint. In 46 anesthetized rats, extracellular single-unit recordings were made from 119 central amygdala neurons that were activated orthodromically by electrical stimulation in the lateral pontine parabrachial area and were tested for receptive fields in the knee joints. Responses to brief mechanical stimulation of joints, muscles, and skin and to cutaneous thermal stimuli were recorded. Receptive-field sizes and thresholds were mapped and stimulus-response functions constructed. Neurons in the central nucleus of the amygdala with excitatory input from the knee joint ( n = 62) typically had large symmetrical receptive fields in both hindlimbs or in all four extremities and responded exclusively or preferentially to noxious mechanical stimulation of deep tissue ( n = 58). Noxious mechanical stimulation of the skin excited 30 of these neurons; noxious heat activated 21 neurons. Stimulus-response data were best fitted by a sigmoid nonlinear regression model rather than by a monotonically increasing linear function. Another 15 neurons were inhibited by noxious mechanical stimulation of the knee joint and other deep tissue. Fifteen neurons had no receptive field in the knee but responded to noxious stimulation of other body areas; 27 nonresponsive neurons were not activated by natural somesthetic stimulation. Our data suggest that excitation is the predominant effect of brief painful stimulation of somatic tissue on the population of central amygdala neurons with knee joint input. Their large symmetrical receptive fields and sigmoid rather than monotonically increasing linear stimulus-response functions suggest a role of nociceptive central amygdala neurons in other than sensory-discriminative aspects of pain.


2002 ◽  
Vol 953 (1-2) ◽  
pp. 101-111 ◽  
Author(s):  
Dorothy E.F McKeegan ◽  
Theodorus G.M Demmers ◽  
Christopher M Wathes ◽  
R Bryan Jones ◽  
Michael J Gentle

NeuroImage ◽  
1998 ◽  
Vol 8 (2) ◽  
pp. 140-148 ◽  
Author(s):  
C. Büchel ◽  
A.P. Holmes ◽  
G. Rees ◽  
K.J. Friston

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