Prostaglandin E2-induced sensitization of the heat response of canine visceral polymodal receptors in vitro

Mizumura, Kazue; Minagawa, Munenori; Tsujii, Yoichiro; Kumazawa, Takao

doi:10.1016/0304-3940(93)90154-d

Cited by 51 publications

(28 citation statements)

References 14 publications

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“…In addition, prostaglandin E2, histamine (Koda and Mizumura 2002), and ATP (Page et al 2000) are known to sensitize nociceptor responses to mechanical stimulus. All these substances also sensitize nociceptors to heat (Koda et al 1996;Kress and Guenther 1999;Mizumura et al 1993;Petho et al 2001;Yajima et al 2005), although the concentration needed to sensitize sensory receptors to mechanical stimulus is higher than that needed to sensitize them to heat (Koda et al 2002). This result might suggest that the above substances are unlikely to be responsible for the sensitization to mechanical stimulus in the ECC group because the heat sensitivities were not altered in the present experiment.…”

Section: Effects Of Eccmentioning

confidence: 51%

Augmented Mechanical Response of Muscle Thin-Fiber Sensory Receptors Recorded from Rat Muscle–Nerve Preparations In Vitro After Eccentric Contraction

Taguchi¹,

Sato²,

Mizumura³

2005

Journal of Neurophysiology

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114

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Taguchi, Toru, Jun Sato, and Kazue Mizumura. Augmented mechanical response of muscle thin-fiber sensory receptors recorded from rat muscle-nerve preparations in vitro after eccentric contraction. J Neurophysiol 94: 2822Neurophysiol 94: -2831Neurophysiol 94: , 2005 doi:10.1152/jn.00470.2005. Unaccustomed strenuous exercise, especially that from eccentric muscular work, often causes muscle tenderness, which is a kind of mechanical hyperalgesia. We developed an animal model of delayed-onset muscle soreness (DOMS) from eccentric muscular contraction (ECC) in rats and demonstrated the existence of muscle tenderness by means of behavioral pain tests and c-Fos protein expression in the spinal dorsal horn. The purpose of the present study was to examine whether the sensitivities of muscle thin-fiber sensory receptors to mechanical, chemical, and thermal stimuli were altered after repetitive ECC in a rat model of DOMS. ECC was caused in the animals by electrical stimulation of the common peroneal nerve innervating the extensor digitorum longus muscle (EDL) while the muscle was being stretched. Activities of single thin-fiber receptors (sensitive to pressure but insensitive to stretch, with conduction velocity slower than 2.0 m/s) were recorded from muscle (EDL)-nerve preparations in vitro 2 days after ECC when mechanical hyperalgesia was at its peak. The mechanical threshold of thin-fiber receptors was found to be very much lower in the ECC preparations than in the nontreated control (CTR) [median 65.4 mN (interquartile range [IQR]; 46.6 -122.0 mN) in the CTR preparation vs. 38.2 mN (IQR; 26.8 -55.8 mN) in the ECC, P Ͻ 0.001]. In addition, the total number of evoked discharges during a ramp mechanical stimulus, taken as an index of the magnitude of the mechanical response, nearly doubled in the ECC preparations compared with the CTR [24.7 spikes (IQR; 14.2-37.1 spikes) in the CTR preparation vs. 54.2 spikes (IQR; 24.3-89.0 spikes) in the ECC, P Ͻ 0.001]. In contrast, the numbers of discharges induced by chemical (pH 5.5, lactic acid, adenosine triphosphate, and bradykinin) and thermal (cold and heat) stimuli were not different between the two preparations. These results suggest that augmentation of the mechanical response in muscle thin-fiber sensory receptors might be related to the muscle tenderness in DOMS after ECC.

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Section: Effects Of Eccmentioning

confidence: 51%

Augmented Mechanical Response of Muscle Thin-Fiber Sensory Receptors Recorded from Rat Muscle–Nerve Preparations In Vitro After Eccentric Contraction

Taguchi¹,

Sato²,

Mizumura³

2005

Journal of Neurophysiology

Self Cite

114

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“…PGE 2 enhanced the number of discharges evoked by heat stimulation in dog testicular nociceptors in vitro, and this effect was reported to be mediated by EP 2 receptors (389,391,499). In this model, forskolin or dibutyryl cAMP (an analog of cAMP) combined with a PDE inhibitor, also enhanced heat-induced discharge activity (496,499).…”

Section: Prostanoid-induced Sensitization To Heat Stimulimentioning

confidence: 68%

“…In this model, forskolin or dibutyryl cAMP (an analog of cAMP) combined with a PDE inhibitor, also enhanced heat-induced discharge activity (496,499). Also in vitro, in the neonatal rat spinal cord-tail preparation, PGE 1 , PGE 2 , PGF 2␣ and PGI 2 , but not PGD 2 , augmented the heat response of nociceptors (616).…”

Section: Prostanoid-induced Sensitization To Heat Stimulimentioning

confidence: 79%

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Sensory and Signaling Mechanisms of Bradykinin, Eicosanoids, Platelet-Activating Factor, and Nitric Oxide in Peripheral Nociceptors

Pethő

Reeh

2012

Physiological Reviews

244

200

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Peripheral mediators can contribute to the development and maintenance of inflammatory and neuropathic pain and its concomitants (hyperalgesia and allodynia) via two mechanisms. Activation or excitation by these substances of nociceptive nerve endings or fibers implicates generation of action potentials which then travel to the central nervous system and may induce pain sensation. Sensitization of nociceptors refers to their increased responsiveness to either thermal, mechanical, or chemical stimuli that may be translated to corresponding hyperalgesias. This review aims to give an account of the excitatory and sensitizing actions of inflammatory mediators including bradykinin, prostaglandins, thromboxanes, leukotrienes, platelet-activating factor, and nitric oxide on nociceptive primary afferent neurons. Manifestations, receptor molecules, and intracellular signaling mechanisms of the effects of these mediators are discussed in detail. With regard to signaling, most data reported have been obtained from transfected nonneuronal cells and somata of cultured sensory neurons as these structures are more accessible to direct study of sensory and signal transduction. The peripheral processes of sensory neurons, where painful stimuli actually affect the nociceptors in vivo, show marked differences with respect to biophysics, ultrastructure, and equipment with receptors and ion channels compared with cellular models. Therefore, an effort was made to highlight signaling mechanisms for which supporting data from molecular, cellular, and behavioral models are consistent with findings that reflect properties of peripheral nociceptive nerve endings. Identified molecular elements of these signaling pathways may serve as validated targets for development of novel types of analgesic drugs.

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“…It is known that intravesical administration of PGE 2 enhances the micturition reflex (9) and that this effect is mediated in part by lowering the threshold of capsaicin-sensitive bladder afferent nerves (18). PGE 2 has been reported to sensitize peripheral terminals of small-diameter, high-threshold, primary afferent fibers to thermal, chemical, and mechanical stimuli (14,15,21,28). In the present study, we have demonstrated for the first time that an antagonist, DG-041, attenuated the response of afferent nerves to bladder distension, selectively on high-threshold and low-conductivity afferent nerves.…”

Section: Discussionmentioning

confidence: 99%

An excitatory role for peripheral EP₃ receptors in bladder afferent function

Su¹,

Lashinger²,

Leon³

et al. 2008

American Journal of Physiology-Renal Physiology

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The excitatory roles of EP3 receptors at the peripheral afferent nerve innervating the rat urinary bladder have been evaluated by using the selective EP3 antagonist (2E)-3-{1-[(2,4-dichlorophenyl)methyl]-5-fluoro-3-methyl-1H-indol-7-yl}-N-[(4,5-dichloro-2-thienyl)sulfonyl]-2-propenamide (DG-041). The bladder rhythmic contraction model and a bladder pain model measuring the visceromotor reflex (VMR) to urinary bladder distension (UBD) have been used to evaluate DG-041 in female rats. In addition, male rats [spontaneously hypertensive rat (SHR), WistarKyoto (WKY), and Sprague-Dawley (SD)] were anesthetized with pentobarbital sodium, and primary afferent fibers in the L 6 dorsal root were isolated for recording the inhibitory response to UBD following intravenous injection of DG-041. Intravenous injection of DG-041 (10 mg/kg), a peripherally restricted EP 3 receptor antagonist, significantly reduced the frequency of bladder rhythmic contraction and inhibited the VMR response to bladder distension. The magnitude of reduction of the VMR response was not different in the different strains of rats (SD, SHR, and WKY). Furthermore, quantitative characterization of the mechanosensitive properties of bladder afferent nerves in SHR, WKY, and SD rats did not show the SHR to be supersensitive to bladder distension. DG-041 selectively attenuated responses of mechanosensitive afferent nerves to UBD, with strong suppression on the slow-conducting, high-threshold afferent fibers, with equivalent activity in the three strains. We conclude that sensitization of afferent nerve activity was not one of the mechanisms of bladder hypersensitivity in SHR. EP 3 receptors are involved in the regulation of bladder micturition and bladder nociception at the peripheral level.EP3; viscermotor reflex; bladder rhythmic contraction; bladder distension; afferent nerve SENSATION ASSOCIATED WITH the urinary bladder is conveyed primarily by pelvic and hypogastric nerves, by which the signal is relayed to the central nervous system (CNS). Most afferent fibers innervating the musculature of the bladder body pass through the pelvic nerve, whereas the majority of afferent endings in the bladder submucosa are derived from the hypogastric nerve (41), suggesting that the afferent fibers in the pelvic and hypogastric nerves have different roles, signaling mechanical stimulation (e.g., bladder distension) and chemical stimulation (e.g., inflammation), respectively (20,22,30,34). Bladder distension is a natural mechanical stimulus to evoke sensations such as fullness, urgency, and pain while the literature suggests a complex regulatory role of prostaglandins (PGs) in multiple aspects of urinary bladder physiology/pathophysiology. PGE 2 , one of the principal PGs, is synthesized in urothelium and detrusor smooth muscle (19,24,25,27) as well as in neurons and glial cells (18,23) and is released in response to various physiological (e.g., bladder distension) and pathological (e.g., mediators of inflammation) stimulation. PGE 2 interacts with four EP receptor subt...

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Prostaglandin E2-induced sensitization of the heat response of canine visceral polymodal receptors in vitro

Cited by 51 publications

References 14 publications

Augmented Mechanical Response of Muscle Thin-Fiber Sensory Receptors Recorded from Rat Muscle–Nerve Preparations In Vitro After Eccentric Contraction

Augmented Mechanical Response of Muscle Thin-Fiber Sensory Receptors Recorded from Rat Muscle–Nerve Preparations In Vitro After Eccentric Contraction

Sensory and Signaling Mechanisms of Bradykinin, Eicosanoids, Platelet-Activating Factor, and Nitric Oxide in Peripheral Nociceptors

An excitatory role for peripheral EP₃ receptors in bladder afferent function

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Prostaglandin E2-induced sensitization of the heat response of canine visceral polymodal receptors in vitro

Cited by 51 publications

References 14 publications

Augmented Mechanical Response of Muscle Thin-Fiber Sensory Receptors Recorded from Rat Muscle–Nerve Preparations In Vitro After Eccentric Contraction

Augmented Mechanical Response of Muscle Thin-Fiber Sensory Receptors Recorded from Rat Muscle–Nerve Preparations In Vitro After Eccentric Contraction

Sensory and Signaling Mechanisms of Bradykinin, Eicosanoids, Platelet-Activating Factor, and Nitric Oxide in Peripheral Nociceptors

An excitatory role for peripheral EP3 receptors in bladder afferent function

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Resources

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An excitatory role for peripheral EP₃ receptors in bladder afferent function