Nociceptive effects induced by intrathecal administration of prostaglandin D2, E2, or F2α to conscious mice

Uda, Rumiko; Horiguchi, S; Ito, Seiji; Hyodo, Masayoshi; Hayaishi, Osamu

doi:10.1016/0006-8993(90)90723-o

Cited by 169 publications

(71 citation statements)

References 32 publications

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“…A functional role for prostaglandins in the spinal cord has been confirmed by intrathecal administration of COX products such as PGE2, PGD~ and PGF2a [23,24]. Evidence has also been presented for spinal actions of NSAIDs, which are known to inhibit COX function [25].…”

Section: Discussionmentioning

confidence: 99%

Up‐regulation of cyclooxygenase‐2 mRNA in the rat spinal cord following peripheral inflammation

et al. 1996

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Prostaglandins (PG) have been described as mediators in spinal nociceptive processing after peripheral inflammation. Enzymes essential for PG biosynthesis, cyclooxygenase isozymes COX-1 and COX-2, have not yet been investigated in the spinal cord. In two studies on rats with adjuvant-induced peripheral inflammation levels of mRNA expression of both COX isoforms were analyzed in the lumbar section of the spinal curd using reverse transcription-polymerase chain reaction (RT-PCR) technique. We could show that mRNA of both COX isoforms is expressed constitutively in the spinal cord with COX-2 as the predominant isoform. Six hours after induction of peripheral inflammation, levels of COX-2 mRNA expression were raised significantly in respect to untreated control rats and returned to baseline within 3 days after induction of inflammation. COX-2 might therefore be regarded as the COX isozyme responsible for spinal PG release in nociceptive processing under a peripheral inflammatory stimulus.l~ey words: Cyclooxygenase-2; Inflammation; Spinal cord; R F-PCR densa of the kidney [8] the testis or the brain, where COX-2 is not only expressed constitutively but also considered to be the dominating COX isoform [9][10][11]. In the central nervous system (CNS) prostaglandins maintain important functions as neuroregulators [12]. It has been reported that PGs are released from the spinal cord by various processes as stimulation of afferent nerves [13], noxious thermal stimulation [14] and by increased potassium levels [15]. Prostaglandins are also known to be involved in transmission of nociceptive information in the spinal cord after peripheral inflammation [16]. Functional evidence thus indicates a role for cyclooxygenases in the spinal cord, expression of the enzyme itself, however, has not yet been investigated. We conducted two studies to determine the spinal presence and distribution of COX isozymes using the rat model of adjuvant-induced inflammation. Tissue samples of hindpaws and the lumbar section of the spinal cord were taken before and after induction of inflammation and examined for levels of COX mRNA expression by reverse transcription-polymerase chain reaction (RT-PCR).

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Section: Discussionmentioning

confidence: 99%

Up‐regulation of cyclooxygenase‐2 mRNA in the rat spinal cord following peripheral inflammation

et al. 1996

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“…Because there is evidence that prostaglandin E 2 (PGE 2 ) sensitizes primary afferent nociceptors and produces allodynia via a cAM Pdependent pathway (Ferreira and Nakamura, 1979;Taiwo et al, 1989;Taiwo and Levine, 1991), we studied the effect of intraplantar injection of PGE 2 on thermal and mechanical nociceptive thresholds. We also examined the effect of spinal administration of PGE 2 in mutant and wild-type mice, because it has been shown that spinal injections of PGE 2 evokes a profound hyperalgesia and allodynia Levine, 1986, 1988;Uda et al, 1990;Minami et al, 1994a,b;Malmberg et al, 1995). A total dose of 0.1 g of PGE 2 delivered in a volume of 5.0 l was administered either into the plantar surface of the paw or intrathecally, by lumbar puncture, according to the method of Hylden and Wilcox (1980).…”

Section: Methodsmentioning

confidence: 99%

Diminished Inflammation and Nociceptive Pain with Preservation of Neuropathic Pain in Mice with a Targeted Mutation of the Type I Regulatory Subunit of cAMP-Dependent Protein Kinase

et al. 1997

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To assess the contribution of PKA to injury-induced inflammation and pain, we evaluated nociceptive responses in mice that carry a null mutation in the gene that encodes the neuronalspecific isoform of the type I regulatory subunit (RI␤) of PKA. Acute pain indices did not differ in the RI␤ PKA mutant mice compared with wild-type controls. However, tissue injuryevoked persistent pain behavior, inflammation of the hindpaw, and ipsilateral dorsal horn Fos immunoreactivity was significantly reduced in the mutant mice, as was plasma extravasation induced by intradermal injection of capsaicin into the paw. The enhanced thermal sensitivity observed in wild-type mice after intraplantar or intrathecal (spinal) administration of prostaglandin E 2 was also reduced in mutant mice. In contrast, indices of pain behavior produced by nerve injury were not altered in the mutant mice. Thus, RI␤ PKA is necessary for the full expression of tissue injury-evoked (nociceptive) pain but is not required for nerve injury-evoked (neuropathic) pain. Because the RI␤ subunit is only present in the nervous system, including small diameter trkA receptor-positive dorsal root ganglion cells, we suggest that in inflammatory conditions, RI␤ PKA is specifically required for nociceptive processing in the terminals of small-diameter primary afferent fibers.

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“…The biological effects of PGD 2 are usually mediated by its two G protein-coupled receptors: D-type prostanoid receptor 1 (DP 1 ) and D-type prostanoid receptor 2 (DP 2 ), also known as chemoattractant homologous receptor expressed on Th2 cells (CRTH2). PGD 2 has been recognized to regulate central (14,28) and peripheral (3,10,15) nerve functions. These neuronal regulation effects are mediated mainly through the DP 1 receptor (17,27), but the effect of PGD 2 on sensory afferents in the GI tract is largely unknown.…”

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confidence: 99%

Role of prostaglandin D₂ in mast cell activation-induced sensitization of esophageal vagal afferents

Zhang

Grabauskas

Joo

et al. 2013

American Journal of Physiology-Gastrointestinal and Liver Physi

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S. Role of prostaglandin D 2 in mast cell activationinduced sensitization of esophageal vagal afferents. Am J Physiol Gastrointest Liver Physiol 304: G908 -G916, 2013. First published March 7, 2013 doi:10.1152/ajpgi.00448.2012.-Sensitization of esophageal afferents plays an important role in esophageal nociception, but the mechanism is less clear. Our previous studies demonstrated that mast cell (MC) activation releases the preformed mediators histamine and tryptase, which play important roles in sensitization of esophageal vagal nociceptive C fibers. PGD 2 is a lipid mediator released by activated MCs. Whether PGD2 plays a role in this sensitization process has yet to be determined. Expression of the PGD 2 DP1 and DP2 receptors in nodose ganglion neurons was determined by immunofluorescence staining, Western blotting, and RT-PCR. Extracellular recordings were performed in ex vivo esophageal-vagal preparations. Action potentials evoked by esophageal distension were compared before and after perfusion of PGD 2, DP1 and DP2 receptor agonists, and MC activation, with or without pretreatment with antagonists. The effect of PGD2 on 1,1=-dioctadecyl-3,3,3=,3=-tetramethylindocarbocyanine perchlorate (DiI)-labeled esophageal nodose neurons was determined by patch-clamp recording. Our results demonstrate that DP1 and DP2 receptor mRNA and protein were expressed mainly in small-and medium-diameter neurons in nodose ganglia. PGD2 significantly increased esophageal distension-evoked action potential discharges in esophageal nodose C fibers. The DP1 receptor agonist BW 245C mimicked this effect. PGD2 directly sensitized DiI-labeled esophageal nodose neurons by decreasing the action potential threshold. Pretreatment with the DP1 receptor antagonist BW A868C significantly inhibited PGD2 perfusion-or MC activation-induced increases in esophageal distensionevoked action potential discharges in esophageal nodose C fibers. In conclusion, PGD2 plays an important role in MC activation-induced sensitization of esophageal nodose C fibers. This adds a novel mechanism of visceral afferent sensitization.

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Nociceptive effects induced by intrathecal administration of prostaglandin D2, E2, or F2α to conscious mice

Cited by 169 publications

References 32 publications

Up‐regulation of cyclooxygenase‐2 mRNA in the rat spinal cord following peripheral inflammation

Up‐regulation of cyclooxygenase‐2 mRNA in the rat spinal cord following peripheral inflammation

Diminished Inflammation and Nociceptive Pain with Preservation of Neuropathic Pain in Mice with a Targeted Mutation of the Type I Regulatory Subunit of cAMP-Dependent Protein Kinase

Role of prostaglandin D₂ in mast cell activation-induced sensitization of esophageal vagal afferents

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Nociceptive effects induced by intrathecal administration of prostaglandin D2, E2, or F2α to conscious mice

Cited by 169 publications

References 32 publications

Up‐regulation of cyclooxygenase‐2 mRNA in the rat spinal cord following peripheral inflammation

Up‐regulation of cyclooxygenase‐2 mRNA in the rat spinal cord following peripheral inflammation

Diminished Inflammation and Nociceptive Pain with Preservation of Neuropathic Pain in Mice with a Targeted Mutation of the Type I Regulatory Subunit of cAMP-Dependent Protein Kinase

Role of prostaglandin D2 in mast cell activation-induced sensitization of esophageal vagal afferents

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Role of prostaglandin D₂ in mast cell activation-induced sensitization of esophageal vagal afferents