scholarly journals Involvement of Peripheral Purinoceptors in Sympathetic Modulation of Capsaicin-Induced Sensitization of Primary Afferent Fibers

2006 ◽  
Vol 96 (5) ◽  
pp. 2207-2216 ◽  
Author(s):  
Yong Ren ◽  
Xiaoju Zou ◽  
Li Fang ◽  
Qing Lin
Keyword(s):  
Receptor Agonist ◽  
P2x Receptors ◽  
Intradermal Injection ◽  
Disulfonic Acid ◽  
Mechanical Stimuli ◽  
Primary Afferent ◽  
C Fibers ◽  
Afferent Fibers ◽  
Sympathetic Modulation ◽  
Primary Afferent Fibers

Purinoceptors are distributed in primary afferent terminals, where transmission of nociceptive information is modulated by these receptors. In the present study, we evaluated whether the activation or blockade of purinoceptors of subtypes P2X and P2Y in the periphery affected the sensitization of primary afferents induced by intradermal injection of capsaicin (CAP) and examined their role in sympathetic modulation of sensitization of primary nociceptive afferents. Afferent activity was recorded from single Aδ- and C-primary afferent fibers in the tibial nerve in anesthetized rats. Peripheral pretreatment with α,β-methylene adenosine 5′-triphosphate (α,β-meATP), a P2X-selective receptor agonist, could potentiate the CAP-induced enhancement of responses of Aδ- and C-primary afferent nociceptive fibers to mechanical stimuli in sympathetically intact rats. After sympathetic denervation, the enhanced responses of both Aδ- and C-fibers after CAP injection were dramatically reduced. However, this reduction could be restored when P2X receptors were activated by α,β-meATP. A blockade of P2X receptors by pyridoxalphosphate-6-azophenyl-2′,4′-disulfonic acid could significantly reduce the CAP-induced sensitization of Aδ- and C-fibers. Pretreatment with uridine 5′-triphosphate, a P2Y-selective receptor agonist, did not significantly affect or restore the CAP-induced sensitization of Aδ- and C-fibers under sympathetically intact or sympathectomized conditions. Our study supports the view that ATP plays a role in modulation of primary afferent nociceptor sensitivity mainly by P2X receptors. Combined with our previous study, our data also provide further evidence that the sensitization of primary afferent nociceptors is subject to sympathetic modulation by activation of P2X as well as α1-adrenergic receptors.

Sympathetic Modulation of Activity in Aδ- and C-Primary Nociceptive Afferents After Intradermal Injection of Capsaicin in Rats

2005 ◽  
Vol 93 (1) ◽  
pp. 365-377 ◽  
Author(s):  
Yong Ren ◽  
Xiaoju Zou ◽  
Li Fang ◽  
Qing Lin
Keyword(s):  
Adrenergic Receptors ◽  
Intradermal Injection ◽  
Mechanical Stimuli ◽  
Primary Afferent ◽  
C Fibers ◽  
Afferent Fibers ◽  
Sympathetic Modulation ◽  
Primary Afferent Fibers ◽  
Sympathetic Efferents ◽  
Intact Rats

Neuropathic and inflammatory pain can be modulated by the sympathetic nervous system. In some pain models, sympathetic postganglionic efferents are involved in the modulation of nociceptive transmission in the periphery. The purpose of this study is to examine the sensitization of Aδ- and C-primary afferent nociceptors induced by intradermal injection of capsaicin (CAP) to see whether the presence of sympathetic efferents is essential for the sensitization. Single primary afferent discharges were recorded from the tibial nerve after the fiber types were identified by conduction velocity in anesthetized rats. An enhanced response of some Aδ- and most C-primary afferent fibers to mechanical stimuli was seen in sham-sympathectomized rats after CAP (1%, 15 μl) injection, but the enhanced responses of both Aδ- and C-fibers were reduced after sympathetic postganglionic efferents were removed. Peripheral pretreatment with norepinephrine by intraarterial injection could restore and prolong the CAP-induced enhancement of responses under sympathectomized conditions. In sympathetically intact rats, pretreatment with an α1-adrenergic receptor antagonist (terazosin) blocked completely the enhanced responses of C-fibers after CAP injection in sympathetically intact rats without significantly affecting the enhanced responses of Aδ-fibers. In contrast, a blockade of α2-adrenergic receptors by yohimbine only slightly reduced the CAP-evoked enhancement of responses. We conclude that the presence of sympathetic efferents is essential for the CAP-induced sensitization of Aδ- and C-primary afferent fibers to mechanical stimuli and that α1-adrenergic receptors play a major role in the sympathetic modulation of C-nociceptor sensitivity in the periphery.

Sympathetic Influence on Capsaicin-Evoked Enhancement of Dorsal Root Reflexes in Rats

2004 ◽  
Vol 92 (4) ◽  
pp. 2017-2026 ◽  
Author(s):  
Jing Wang ◽  
Yong Ren ◽  
Xiaoju Zou ◽  
Li Fang ◽  
William D. Willis ◽  
...  
Keyword(s):  
Dorsal Root ◽  
Neurogenic Inflammation ◽  
Intradermal Injection ◽  
Primary Afferent ◽  
Adrenoceptor Antagonist ◽  
Afferent Fibers ◽  
Adrenoceptor Agonist ◽  
Sympathetic Modulation ◽  
Sympathetic Influence ◽  
Series Of Experiments

A series of experiments by our group suggest that the initiation and development of neurogenic inflammation in rats are mainly mediated by dorsal root reflexes (DRRs), which are conducted centrifugally from the spinal dorsal horn in primary afferent nocieptors. In this study, DRRs were recorded in anesthetized rats from single afferent fibers in the proximal ends of cut dorsal root filaments at the L4–L6 level and tested for responses to intradermal injection of capsaicin. Sympathectomy combined with pharmacological manipulations were employed to determine if the capsaicin-evoked enhancement of DRRs was subject to sympathetic modulation. DRRs could be recorded from both myelinated (Aβ and Aδ) and unmyelinated (C) afferent fibers. After capsaicin was injected intradermally into the plantar foot, a significant enhancement of DRRs was seen in C- and Aδ-fibers but not in Aβ-fibers. This enhancement of DRRs evoked by capsaicin injection was almost completely prevented by sympathectomy. However, if peripheral α1-adrenoceptors were activated by intra-arterial injection of phenylephrine, the enhancement of DRRs evoked by capsaicin could be restored, whereas no such restoration was seen following pretreatment with an α2-adrenoceptor agonist, UK14,304. Under sympathetically intact conditions, the enhanced DRRs following capsaicin injection could be blocked by administration of terazosin, an α1-adrenoceptor antagonist, but not by administration of yohimbine, an α2-adrenoceptor antagonist. These results provide further evidence that the DRR-mediated neurogenic inflammation depends in part on intact sympathetic efferents acting on peripheral α1-adrenoceptors, which augment the sensitization of primary afferent nociceptors induced by capsaicin injection, helping trigger DRRs that produce vasodilation.

Neurogenic hyperalgesia: the search for the primary cutaneous afferent fibers that contribute to capsaicin-induced pain and hyperalgesia

1991 ◽  
Vol 66 (1) ◽  
pp. 212-227 ◽  
Author(s):  
T. K. Baumann ◽  
D. A. Simone ◽  
C. N. Shain ◽  
R. H. LaMotte
Keyword(s):  
Injection Site ◽  
Intradermal Injection ◽  
Mechanical Stimuli ◽  
Primary Afferent ◽  
Cutaneous Injury ◽  
Afferent Fibers ◽  
Before And After ◽  
Primary Hyperalgesia ◽  
Nociceptive Fibers ◽  
Surrounding Skin

1. A local cutaneous injury can produce primary hyperalgesia within the injured area and secondary hyperalgesia in the normal surrounding skin. An intradermal injection of capsaicin in humans causes intense pain and hyperalgesia to heat and to mechanical stimuli in the surrounding skin. Psychophysical studies in humans supported the conclusions that the hyperalgesia was predominantly the secondary type and depended on one set of neurons sensitizing another (“neurogenic hyperalgesia”) and that the latter set of neurons is located in the central and not the peripheral nervous system. To further test this hypothesis and to search for peripheral neural mechanisms contributing to the pain and neurogenic hyperalgesia from a local injury, we performed neurophysiological experiments in the monkey (Macaca fascicularis) and recorded the responses of cutaneous primary afferent fibers to an intradermal injection of capsaicin and to mechanical and heat stimuli delivered before and after the injection. 2. Most C- and A-fiber mechanoheat-sensitive nociceptive afferent fibers (CMHs and AMHs, respectively) responded too weakly or transiently to capsaicin to account quantitatively for the magnitude of capsaicin pain. Of the known primary afferents tested with capsaicin injections, only the responses of heat-selective nociceptors could potentially account for the pain measured psychophysically in the human. In addition, a novel type of primary afferent--tentatively termed “chemonociceptive”--may have contributed as well. 3. Nociceptive fibers did not become sensitized to either mechanical or heat stimulation after an injection of capsaicin either outside, adjacent to, or inside the receptive field (RF); any changes that occurred could not explain the hyperalgesia to mechanical or heat stimuli observed in humans. 4. The depressed responsiveness ("desensitization") of both myelinated and unmyelinated nociceptive fibers in the monkey to heat and/or mechanical stimulation of the injection site after capsaicin was injected inside their RFs correlated with the analgesia observed at the capsaicin injection site in the human. 5. Capsaicin, topically applied to the RF in a vehicle of dimethyl sulfoxide or alcohol, excited CMHs and AMHs and enhanced the responses of some of these fibers to heat and/or to stroking the skin. In some cases, similar results were produced by the vehicle alone. However, capsaicin and not the vehicle lowered the thresholds of some CMHs to heat. Thus the sensitization of CMHs contributes to the primary hyperalgesia known to occur within the area of skin directly exposed to topically applied capsaicin.(ABSTRACT TRUNCATED AT 400 WORDS)

Aδ and C Primary Afferents Convey Dorsal Root Reflexes After Intradermal Injection of Capsaicin in Rats

2000 ◽  
Vol 84 (5) ◽  
pp. 2695-2698 ◽  
Author(s):  
Qing Lin ◽  
Xiaoju Zou ◽  
William D. Willis
Keyword(s):  
Dorsal Root ◽  
Neurogenic Inflammation ◽  
Low Frequency ◽  
Intradermal Injection ◽  
Spontaneous Firing ◽  
C Fibers ◽  
Dorsal Root Reflex ◽  
Afferent Fibers ◽  
Primary Afferent Fibers ◽  
Aβ Fibers

Antidromic activity was recorded in anesthetized rats from single afferent fibers in the proximal ends of cut dorsal root filaments at the L4–6 level and tested for responses to acute cutaneous inflammation produced by intradermal injection of capsaicin. This antidromic activity included low-frequency spontaneous firing and dorsal root reflex (DRR) discharges evoked by applying von Frey hairs to the skin of the foot. DRRs could be recorded from both small myelinated (Aδ) and unmyelinated (C) afferent fibers, as well as from large myelinated (Aβ) fibers. After capsaicin was injected intradermally into the plantar skin of the foot, a significant enhancement of DRR activity was seen in Aδ and C fibers but not in Aβ fibers, and this increase lasted for ∼1 h. This study supports the hypothesis that centrally mediated antidromic activity in Aδ and C primary afferent fibers contributes to the development of neurogenic inflammation, presumably by release of inflammatory substances in the periphery.

Characterization of Cutaneous Primary Afferent Fibers Excited by Acetic Acid in a Model of Nociception in Frogs

2003 ◽  
Vol 90 (2) ◽  
pp. 566-577 ◽  
Author(s):  
Darryl T. Hamamoto ◽  
Donald A. Simone
Keyword(s):  
Acetic Acid ◽  
Hind Limb ◽  
Receptive Fields ◽  
Primary Afferent ◽  
Exposed Skin ◽  
C Fibers ◽  
Afferent Fibers ◽  
Primary Afferent Fibers ◽  
Low Threshold ◽  
Aβ Fibers

Acetic acid applied to the hind limb of a frog evokes nocifensive behaviors, including a vigorous wiping of the exposed skin, referred to as the wiping response. The aim of this study was to examine the responses of cutaneous primary afferent fibers in frogs to acetic acid (pH 2.84–1.42) applied topically to the skin. Conventional electrophysiological methods were used to record neuronal activity from single identified primary afferent fibers with cutaneous receptive fields on the hind limb. Fibers were classified according to their conduction velocities and responses evoked by mechanical and thermal (heat and cold) stimuli. One hundred and twenty-two mechanosensitive afferent fibers were studied (44 Aβ, 60 Aδ, and 18 C fibers). Thirty-nine percent of all fibers were excited by acetic acid, but a greater percentage of Aδ (52%) and C fibers (44%) were excited than Aβ fibers (20%). Evoked responses of fibers increased with increasingly more acidic pH until the greatest responses were evoked by acetic acid at pH 2.59–2.41. Application of acetic acid at pHs <2.41 evoked less excitation, suggesting that fibers became desensitized. Similar percentages of nociceptors and low-threshold mechanoreceptors were excited by acetic acid. Thus primary afferent fibers were excited by acetic acid at pHs that have been shown to evoke the wiping response in our previous study. The results of the present study suggest that the model of acetic acid-induced nociception in frogs may be useful for studying the mechanisms by which tissue acidosis produces pain.

Primary Afferent Fibers That Contribute to Increased Substance P Receptor Internalization in the Spinal Cord After Injury

1999 ◽  
Vol 81 (3) ◽  
pp. 1379-1390 ◽  
Author(s):  
Brian J. Allen ◽  
Jun Li ◽  
Patrick M. Menning ◽  
Scott D. Rogers ◽  
Joseph Ghilardi ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Electrical Stimulation ◽  
Dorsal Horn ◽  
Nerve Transection ◽  
Primary Afferent ◽  
Lamina I ◽  
C Fibers ◽  
Afferent Fibers ◽  
Primary Afferent Fibers ◽  
Stimulation Of

Primary afferent fibers that contribute to increased substance P receptor internalization in the spinal cord after injury. Upon noxious stimulation, substance P (SP) is released from primary afferent fibers into the spinal cord where it interacts with the SP receptor (SPR). The SPR is located throughout the dorsal horn and undergoes endocytosis after agonist binding, which provides a spatial image of SPR-containing neurons that undergo agonist interaction. Under normal conditions, SPR internalization occurs only in SPR+ cell bodies and dendrites in the superficial dorsal horn after noxious stimulation. After nerve transection and inflammation, SPR immunoreactivity increases, and both noxious as well as nonnoxious stimulation produces SPR internalization in the superficial and deep dorsal horn. We investigated the primary afferent fibers that contribute to enhanced SPR internalization in the spinal cord after nerve transection and inflammation. Internalization evoked by electrical stimulation of the sciatic nerve was examined in untreated animals, at 14 days after sciatic nerve transection or sham surgery and at 3 days after hindpaw inflammation. Electrical stimulation was delivered at intensities to excite Aβ fibers only, Aβ and Aδ fibers or A and C fibers as determined by the compound action potential recorded from the tibial nerve. Electrical stimuli were delivered at a constant rate of 10 Hz for a duration of 5 min. Transection of the sciatic nerve and inflammation produced a 33.7 and 32.5% increase in SPR and immunoreactivity in lamina I, respectively. Under normal conditions, stimulation of Aδ or C fibers evoked internalization that was confined to the superficial dorsal horn. After transection or inflammation, there was a 20–24% increase in the proportion of SPR+ lamina I neurons that exhibited internalization evoked by stimulation of Aδ fibers. The proportion of lamina I SPR+ neurons that exhibited internalization after stimulation of C-fibers was not altered by transection or inflammation because this was nearly maximal under normal conditions. Moreover, electrical stimulation sufficient to excite C fibers evoked SPR internalization in 22% of SPR+ lamina III neurons after nerve transection and in 32–36% of SPR+ neurons in lamina III and IV after inflammation. Stimulation of Aβ fibers alone never evoked internalization in the superficial or deep dorsal horn. These results indicate that activation of small-caliber afferent fibers contributes to the enhanced SPR internalization in the spinal cord after nerve transection and inflammation and suggest that recruitment of neurons that possess the SPR contributes to hyperalgesia.

scholarly journals Opioid Actions in Primary-Afferent Fibers—Involvement in Analgesia and Anesthesia

2011 ◽  
Vol 4 (2) ◽  
pp. 343-365 ◽  
Author(s):  
Eiichi Kumamoto ◽  
Kotaro Mizuta ◽  
Tsugumi Fujita
Keyword(s):  
Primary Afferent ◽  
Afferent Fibers ◽  
Primary Afferent Fibers
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