The development of painful paclitaxel-induced peripheral neuropathy (PIPN) represents a major dose-limiting side effect of paclitaxel chemotherapy. Here we report a promising effect of duvelisib (Copiktra), a novel FDA-approved PI3Kδ/γ isoform-specific inhibitor, in preventing paclitaxel-induced pain-like behavior and pronociceptive signaling in DRGs and spinal cord dorsal horn (SCDH) in rat and mouse model of PIPN. Duvelisib blocked the development of mechanical hyperalgesia in both males and females. Moreover, duvelisib prevented paclitaxel-induced sensitization of TRPV1 receptors, and increased PI3K/Akt signaling in small-diameter DRG neurons and an increase of CD68+ cells within DRGs. Specific optogenetic stimulation of inhibitory neurons combined with patch-clamp recording revealed that duvelisib inhibited paclitaxel-induced weakening of inhibitory, mainly glycinergic control on SCDH excitatory neurons. Enhanced excitatory and reduced inhibitory neurotransmission in the SCDH following PIPN was also alleviated by duvelisib application. In summary, duvelisib showed a promising ability to prevent neuropathic pain in PIPN. The potential use of our findings in human medicine may be augmented by the fact that duvelisib is an FDA-approved drug with known side effects.SIGNIFICANCE STATEMENT We show that duvelisib, a novel FDA-approved PI3Kδ/γ isoform-specific inhibitor, prevents the development of paclitaxel-induced pain-like behavior in males and females and prevents pronociceptive signaling in DRGs and spinal cord dorsal horn in rat and mouse model of paclitaxel-induced peripheral neuropathy.

• Klíčová slova
• PI3K, TRPV1, dorsal horn, glycine, neuropathy, pain,
• MeSH
• bolest MeSH
• fosfatidylinositol-3-kinasy MeSH
• fytogenní protinádorové látky * farmakologie   MeSH
• hyperalgezie chemicky indukované   farmakoterapie   prevence a kontrola   MeSH
• isochinoliny MeSH
• krysa rodu Rattus MeSH
• myši MeSH
• nemoci periferního nervového systému MeSH
• neuralgie * chemicky indukované   farmakoterapie   prevence a kontrola   MeSH
• paclitaxel škodlivé účinky   MeSH
• puriny MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• duvelisib MeSH Prohlížeč
• fytogenní protinádorové látky * MeSH
• isochinoliny MeSH
• paclitaxel MeSH
• puriny MeSH

We aimed to evaluate the regulatory effects of propofol on high-dose remifentanil-induced hyperalgesia. A total of 180 patients receiving laparoscopic cholecystectomy were randomly divided into sevoflurane + high-dose remifentanil (SH) group, sevoflurane + low-dose remifentanil (SL) group and propofol + high-dose remifentanil group (PH) group (n=60). After intravenous administration of midazolam, SH and SL groups were induced with sevoflurane and remifentanil, and PH group was induced with propofol and remifentanil. During anesthesia maintenance, SH and SL groups were given 0.3 microg/kg/min and 0.1 microg/kg/min sevoflurane and remifentanil respectively, and PH group was given 0.3 microg/kg/min propofol and remifentanil. The three groups had significantly different awakening time, extubation time and total dose of remifentanil (P<0.001). Compared with SL group, periumbilical mechanical pain thresholds 6 h and 24 h after surgery significantly decreased in SH group (P<0.05), and the visual analog scale (VAS) scores significantly increased 30 min, 2 h and 6 h after surgery (P<0.05). Compared with SH group, periumbilical mechanical thresholds 6 h and 24 h after surgery were significantly higher in PH group (P<0.05), and VAS scores 30 min, 2 h and 6 h after surgery were significantly lower (P<0.05). PH group first used patient-controlled intravenous analgesia pump significantly later than SL group did (P<0.05). The total consumptions of sufentanil in PH and SL groups were significantly lower than that of SH group (P<0.05). The incidence rates of bradycardia and postoperative chill in PH and SH groups were significantly higher than those of SL group (P<0.05). Anesthesia by infusion of high-dose remifentanil plus sevoflurane caused postoperative hyperalgesia which was relieved through intravenous anesthesia with propofol.

• MeSH
• anestetika inhalační farmakologie   MeSH
• anestetika intravenózní farmakologie   MeSH
• cholecystektomie laparoskopická škodlivé účinky   MeSH
• dospělí MeSH
• hyperalgezie chemicky indukované   prevence a kontrola   MeSH
• lidé středního věku MeSH
• lidé MeSH
• opioidní analgetika aplikace a dávkování   škodlivé účinky   MeSH
• pooperační bolest prevence a kontrola   MeSH
• propofol farmakologie   MeSH
• remifentanil aplikace a dávkování   škodlivé účinky   MeSH
• sevofluran farmakologie   MeSH
• sufentanil aplikace a dávkování   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• randomizované kontrolované studie MeSH
• Názvy látek
• anestetika inhalační MeSH
• anestetika intravenózní MeSH
• opioidní analgetika MeSH
• propofol MeSH
• remifentanil MeSH
• sevofluran MeSH
• sufentanil MeSH

Paclitaxel chemotherapy treatment often leads to neuropathic pain resistant to available analgesic treatments. Recently spinal Toll-like receptor 4 (TLR4) and the transient receptor potential cation channel subfamily V member 1 (TRPV1) were identified to be involved in the pro-nociceptive effect of paclitaxel. The aim of this study was to investigate the role of phosphatidylinositol 3-kinase (PI3K) and serine/threonine kinases in this process, with the use of their antagonists (wortmannin, LY-294002, and staurosporine). The single paclitaxel administration (8 mg/kg i.p.) in mice induced robust mechanical allodynia measured as a reduced threshold to von Frey filament stimulation and generated reduced tachyphylaxis of capsaicin-evoked responses, recorded as changes in mEPSC frequency in patch-clamp recordings of dorsal horn neurons activity in vitro, for up to eight days. Paclitaxel application also induced increased Akt kinase phosphorylation in rat DRG neurons. All these paclitaxel-induced changes were prevented by the wortmannin in vivo pretreatment. Acute co-application of wortmannin or LY-294002 with paclitaxel in spinal cord slices also attenuated the paclitaxel effect on capsaicin-evoked responses. Staurosporine was effective in the acute in vitro experiments and on the first day after the paclitaxel treatment in vivo, but in contrast to wortmannin, it did not have a significant impact later. Our data suggest that the inhibition of PI3K signaling may help alleviate pathological pain syndromes in the paclitaxel-induced neuropathy.

• MeSH
• buňky zadních rohů míšních účinky léků   metabolismus   MeSH
• excitační postsynaptické potenciály účinky léků   MeSH
• fosfatidylinositol-3-kinasy metabolismus   MeSH
• hyperalgezie chemicky indukované   farmakoterapie   metabolismus   MeSH
• inhibitory proteinkinas farmakologie   MeSH
• kapsaicin farmakologie   MeSH
• kationtové kanály TRP MeSH
• kationtové kanály TRPV metabolismus   MeSH
• krysa rodu Rattus MeSH
• lipopolysacharidy farmakologie   MeSH
• mícha účinky léků   metabolismus   MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• neuralgie chemicky indukované   farmakoterapie   metabolismus   MeSH
• onkogenní protein v-akt metabolismus   MeSH
• paclitaxel toxicita   MeSH
• peptidové fragmenty imunologie   metabolismus   MeSH
• potkani Wistar MeSH
• protein-serin-threoninkinasy antagonisté a inhibitory   metabolismus   MeSH
• proteinkinasa C imunologie   metabolismus   MeSH
• signální transdukce účinky léků   MeSH
• toll-like receptor 4 metabolismus   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• inhibitory proteinkinas MeSH
• kapsaicin MeSH
• kationtové kanály TRP MeSH
• kationtové kanály TRPV MeSH
• lipopolysaccharide A MeSH Prohlížeč
• lipopolysacharidy MeSH
• onkogenní protein v-akt MeSH
• paclitaxel MeSH
• peptidové fragmenty MeSH
• protein kinase C (19-31) MeSH Prohlížeč
• protein-serin-threoninkinasy MeSH
• proteinkinasa C MeSH
• toll-like receptor 4 MeSH

Ciguatoxins (CTXs) are marine toxins that cause ciguatera fish poisoning, a debilitating disease dominated by sensory and neurological disturbances that include cold allodynia and various painful symptoms as well as long-lasting pruritus. Although CTXs are known as the most potent mammalian sodium channel activator toxins, the etiology of many of its neurosensory symptoms remains unresolved. We recently described that local application of 1 nM Pacific Ciguatoxin-1 (P-CTX-1) into the skin of human subjects induces a long-lasting, painful axon reflex flare and that CTXs are particularly effective in releasing calcitonin-gene related peptide (CGRP) from nerve terminals. In this study, we used mouse and rat skin preparations and enzyme-linked immunosorbent assays (ELISA) to study the molecular mechanism by which P-CTX-1 induces CGRP release. We show that P-CTX-1 induces CGRP release more effectively in mouse as compared to rat skin, exhibiting EC50 concentrations in the low nanomolar range. P-CTX-1-induced CGRP release from skin is dependent on extracellular calcium and sodium, but independent from the activation of various thermosensory transient receptor potential (TRP) ion channels. In contrast, lidocaine and tetrodotoxin (TTX) reduce CGRP release by 53-75%, with the remaining fraction involving L-type and T-type voltage-gated calcium channels (VGCC). Using transgenic mice, we revealed that the TTX-resistant voltage-gated sodium channel (VGSC) NaV1.9, but not NaV1.8 or NaV1.7 alone and the combined activation of the TTX-sensitive VGSC subtypes NaV1.7 and NaV1.1 carry the largest part of the P-CTX-1-caused CGRP release of 42% and 34%, respectively. Given the contribution of CGRP to nociceptive and itch sensing pathways, our findings contribute to a better understanding of sensory symptoms of acute and chronic ciguatera that may help in the identification of potential therapeutics.

• Klíčová slova
• P-CTX-1, TRPA1, TRPC5, TRPM8, TTX, calcitonin-gene related peptide, ciguatera, neurogenic inflammation, neuropathic pain, tetrodotoxin, voltage-gated calcium channels,
• MeSH
• ciguatera metabolismus   MeSH
• ciguatoxiny chemie   farmakologie   MeSH
• ELISA MeSH
• hyperalgezie chemicky indukované   MeSH
• krysa rodu Rattus MeSH
• lidé MeSH
• lidokain farmakologie   MeSH
• membránové potenciály účinky léků   MeSH
• mořské toxiny farmakologie   MeSH
• myši transgenní MeSH
• myši MeSH
• napětím řízený sodíkový kanál, typ 1 účinky léků   MeSH
• napětově řízený sodíkový kanál typ 11 účinky léků   MeSH
• napěťově řízený sodíkový kanál, typ 9 účinky léků   MeSH
• peptid spojený s genem pro kalcitonin účinky léků   MeSH
• receptory peptidu se vztahem ke genu kalcitoninu účinky léků   MeSH
• tetrodotoxin farmakologie   MeSH
• vápník metabolismus   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• lidé MeSH
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• CALCA protein, human MeSH Prohlížeč
• ciguatoxiny MeSH
• lidokain MeSH
• mořské toxiny MeSH
• napětím řízený sodíkový kanál, typ 1 MeSH
• napětově řízený sodíkový kanál typ 11 MeSH
• napěťově řízený sodíkový kanál, typ 9 MeSH
• peptid spojený s genem pro kalcitonin MeSH
• receptory peptidu se vztahem ke genu kalcitoninu MeSH
• tetrodotoxin MeSH
• vápník MeSH

Crotalphine is a structural analogue to a novel analgesic peptide that was first identified in the crude venom from the South American rattlesnake Crotalus durissus terrificus. Although crotalphine's analgesic effect is well established, its direct mechanism of action remains unresolved. The aim of the present study was to investigate the effect of crotalphine on ion channels in peripheral pain pathways. We found that picomolar concentrations of crotalphine selectively activate heterologously expressed and native TRPA1 ion channels. TRPA1 activation by crotalphine required intact N-terminal cysteine residues and was followed by strong and long-lasting desensitization of the channel. Homologous desensitization of recombinant TRPA1 and heterologous desensitization in cultured dorsal root ganglia neurons was observed. Likewise, crotalphine acted on peptidergic TRPA1-expressing nerve endings ex vivo as demonstrated by suppression of calcitonin gene-related peptide release from the trachea and in vivo by inhibition of chemically induced and inflammatory hypersensitivity in mice. The crotalphine-mediated desensitizing effect was abolished by the TRPA1 blocker HC030031 and absent in TRPA1-deficient mice. Taken together, these results suggest that crotalphine is the first peptide to mediate antinociception selectively and at subnanomolar concentrations by targeting TRPA1 ion channels.

• MeSH
• akční potenciály účinky léků   MeSH
• analgetika farmakologie   terapeutické užití   MeSH
• bradykinin toxicita   MeSH
• HEK293 buňky MeSH
• hyperalgezie chemicky indukované   farmakoterapie   etiologie   MeSH
• kationtové kanály TRP antagonisté a inhibitory   genetika   metabolismus   MeSH
• kationtový kanál TRPA1 MeSH
• kultivované buňky MeSH
• lidé MeSH
• modely nemocí na zvířatech MeSH
• mutace genetika   MeSH
• myši inbrední C57BL MeSH
• myši knockoutované MeSH
• myši MeSH
• neurony účinky léků   metabolismus   MeSH
• peptidy farmakologie   terapeutické užití   MeSH
• spinální ganglia cytologie   MeSH
• vápník metabolismus   MeSH
• zánět komplikace   MeSH
• zvířata MeSH
• zymosan toxicita   MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• analgetika MeSH
• bradykinin MeSH
• crotalphine MeSH Prohlížeč
• kationtové kanály TRP MeSH
• kationtový kanál TRPA1 MeSH
• peptidy MeSH
• Trpa1 protein, mouse MeSH Prohlížeč
• vápník MeSH
• zymosan MeSH

Peripheral neuropathy is dose limiting in paclitaxel cancer chemotherapy and can result in both acute pain during treatment and chronic persistent pain in cancer survivors. The hypothesis tested was that paclitaxel produces these adverse effects at least in part by sensitizing transient receptor potential vanilloid subtype 1 (TRPV1) through Toll-like receptor 4 (TLR4) signaling. The data show that paclitaxel-induced behavioral hypersensitivity is prevented and reversed by spinal administration of a TRPV1 antagonist. The number of TRPV1(+) neurons is increased in the dorsal root ganglia (DRG) in paclitaxel-treated rats and is colocalized with TLR4 in rat and human DRG neurons. Cotreatment of rats with lipopolysaccharide from the photosynthetic bacterium Rhodobacter sphaeroides (LPS-RS), a TLR4 inhibitor, prevents the increase in numbers of TRPV1(+) neurons by paclitaxel treatment. Perfusion of paclitaxel or the archetypal TLR4 agonist LPS activated both rat DRG and spinal neurons directly and produced acute sensitization of TRPV1 in both groups of cells via a TLR4-mediated mechanism. Paclitaxel and LPS sensitize TRPV1 in HEK293 cells stably expressing human TLR4 and transiently expressing human TRPV1. These physiological effects also are prevented by LPS-RS. Finally, paclitaxel activates and sensitizes TRPV1 responses directly in dissociated human DRG neurons. In summary, TLR4 was activated by paclitaxel and led to sensitization of TRPV1. This mechanism could contribute to paclitaxel-induced acute pain and chronic painful neuropathy. Significance statement: In this original work, it is shown for the first time that paclitaxel activates peripheral sensory and spinal neurons directly and sensitizes these cells to transient receptor potential vanilloid subtype 1 (TRPV1)-mediated capsaicin responses via Toll-like receptor 4 (TLR4) in multiple species. A direct functional interaction between TLR4 and TRPV1 is shown in rat and human dorsal root ganglion neurons, TLR4/TRPV1-coexpressing HEK293 cells, and in both rat and mouse spinal cord slices. Moreover, this is the first study to show that this interaction plays an important role in the generation of behavioral hypersensitivity in paclitaxel-related neuropathy. The key translational implications are that TLR4 and TRPV1 antagonists may be useful in the prevention and treatment of chemotherapy-induced peripheral neuropathy in humans.

• Klíčová slova
• DRG, cancer, dorsal horn, neuropathy,
• MeSH
• excitační postsynaptické potenciály účinky léků   MeSH
• fytogenní protinádorové látky antagonisté a inhibitory   farmakologie   MeSH
• HEK293 buňky MeSH
• hyperalgezie chemicky indukované   patofyziologie   MeSH
• kationtové kanály TRPV antagonisté a inhibitory   MeSH
• krysa rodu Rattus MeSH
• lidé MeSH
• měření bolesti účinky léků   MeSH
• metoda terčíkového zámku MeSH
• mícha účinky léků   MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• nervové receptory účinky léků   MeSH
• paclitaxel antagonisté a inhibitory   farmakologie   MeSH
• potkani Sprague-Dawley MeSH
• signální transdukce účinky léků   MeSH
• spinální ganglia cytologie   účinky léků   MeSH
• toll-like receptor 4 antagonisté a inhibitory   účinky léků   MeSH
• vápník metabolismus   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• lidé MeSH
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• fytogenní protinádorové látky MeSH
• kationtové kanály TRPV MeSH
• paclitaxel MeSH
• toll-like receptor 4 MeSH
• TRPV1 receptor MeSH Prohlížeč
• vápník MeSH

Modulation of nociceptive synaptic transmission in the spinal cord is implicated in the development and maintenance of several pathological pain states. The chemokine CCL2 (C-C motif ligand 2) was shown to be an important factor in the development of neuropathic pain after peripheral nerve injury. In our experiments we have studied the effect of CCL2 application and TRPV1 (transient receptor potential vanilloid 1) receptor activation on nociceptive signaling and the modulation of synaptic transmission. Intrathecal drug application in behavioral experiments and patch-clamp recordings of spontaneous, miniature and dorsal root stimulation-evoked excitatory postsynaptic currents (sEPSCs, mEPSCs, eEPSCs) from superficial dorsal horn neurons in acute rat spinal cord slices were used. The intrathecal application of CCL2 induced thermal hyperalgesia and mechanical allodynia, while pretreatment with the TRPV1 receptor antagonist SB366791 diminished the thermal but not the mechanical hypersensitivity. Patch-clamp experiments showed an increase of sEPSC and mEPSC (124.5 ± 12.8% and 161.2 ± 17.3%, respectively) frequency in dorsal horn neurons after acute CCL2 application. This CCL2-induced increase was prevented by SB366791 pretreatment (89.4 ± 6.0%, 107.5 ± 14.2%). CCL2 application increased the amplitude of eEPSCs (188.1 ± 32.1%); this increase was significantly lower in experiments with SB366791 pretreatment (120.8 ± 17.2%). Our results demonstrate that the activation of spinal TRPV1 receptors plays an important role in the modulation of nociceptive signaling induced by CCL2 application. The mechanisms of cooperation between the CCL2 activated receptors and TRPV1 receptors on the central branches of primary afferent fibers may be especially important during different pathological pain states and need to be further investigated.

• Klíčová slova
• CCL2, EPSC, Pain, Spinal cord, Synaptic transmission, TRPV1,
• MeSH
• anilidy terapeutické užití   MeSH
• buňky zadních rohů míšních účinky léků   fyziologie   MeSH
• časové faktory MeSH
• chemokin CCL2 toxicita   MeSH
• cinnamáty terapeutické užití   MeSH
• excitační postsynaptické potenciály účinky léků   MeSH
• hyperalgezie chemicky indukované   farmakoterapie   metabolismus   MeSH
• kapsaicin farmakologie   MeSH
• kationtové kanály TRPV antagonisté a inhibitory   metabolismus   MeSH
• krysa rodu Rattus MeSH
• látky ovlivňující senzorický systém farmakologie   MeSH
• MAP kinasa-kinasa-kinasa 3 metabolismus   MeSH
• metoda terčíkového zámku MeSH
• mícha cytologie   účinky léků   metabolismus   MeSH
• modely nemocí na zvířatech MeSH
• novorozená zvířata MeSH
• potkani Wistar MeSH
• práh bolesti účinky léků   MeSH
• techniky in vitro MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• anilidy MeSH
• chemokin CCL2 MeSH
• cinnamáty MeSH
• kapsaicin MeSH
• kationtové kanály TRPV MeSH
• látky ovlivňující senzorický systém MeSH
• MAP kinasa-kinasa-kinasa 3 MeSH
• N-(3-methoxyphenyl)-4-chlorocinnamanilide MeSH Prohlížeč
• Trpv1 protein, rat MeSH Prohlížeč

The aim of the present study was to evaluate and compare the analgesic activity and serum levels of meloxicam (CAS 71125-38-7) after administration of meloxicam associated with beta-cyclodextrin (BCD, CAS 7585-39-9) and unmodified meloxicam. The analgesic activity was measured using the plantar test (rats) and the writhing test (mice). In the plantar test, BCD-meloxicam (3 mg/kg and 10 mg/kg orally) showed higher analgesic activity than corresponding doses of meloxicam alone; in the writhing test BCD-meloxicam (7 mg/kg and 15 mg/kg orally) showed stronger analgesic activity than unmodified meloxicam. Serum levels of meloxicam were significantly higher, at 0.5 h and 1 h after administration of BCD-meloxicam orally than those of unmodified meloxicam (both dosed at 10 mg/kg). The present results suggest that association with beta-cyclodextrin increases the analgesic activity of meloxicam. This may be due to an icreased systemic bioavailability of meloxicam after oral administration of its complex with beta-cyclodextrin.

• MeSH
• analgetika farmakologie   MeSH
• antiflogistika nesteroidní krev   farmakologie   MeSH
• beta-cyklodextriny krev   MeSH
• bolest farmakoterapie   MeSH
• hyperalgezie chemicky indukované   MeSH
• karagenan MeSH
• krysa rodu Rattus MeSH
• meloxikam MeSH
• měření bolesti účinky léků   MeSH
• myši MeSH
• potkani Wistar MeSH
• thiaziny krev   farmakologie   MeSH
• thiazoly krev   farmakologie   MeSH
• vény účinky léků   fyziologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• analgetika MeSH
• antiflogistika nesteroidní MeSH
• beta-cyklodextriny MeSH
• betadex MeSH Prohlížeč
• karagenan MeSH
• meloxikam MeSH
• thiaziny MeSH
• thiazoly MeSH

Knowledge on the involvement of spinal COX-1 and COX-2 in pain due to osteoarthritis could be useful for better understanding of its pathogenesis and therapy. In this study we have investigated a long-term pattern of expression and production of spinal COX-1 and COX-2 in the model of osteoarthritis induced in rats by injection of monoiodoacetate (MIA) into the knee joint. MIA injection produced thermal hyperalgesia (assessed by the plantar test) and tactile allodynia (measured with von Frey hairs). The pain measures reached maximum on the fifht day, then remained relatively stable. The expression of spinal COX-2 mRNA reached maximum on day 5 (5.2 times; P<0.001) and remained increased until day 31 (4.9 times; P<0.001). Expression of spinal COX-1 mRNA increased gradually reaching maximum on the day 31 (4.5 times; P<0.001) when the relative expression of both genes was almost equal. The production of both proteins was almost similar at the beginning of the experiment. The highest production of COX-2 protein was observed on day 5 after the induction of osteoarthritis (increased 3.9 times). The levels of COX-1 protein increased gradually with maximum on day 31 (3.4 times). The present findings indicate that not only expression of COX-2 mRNA but also that of COX-1 mRNA is significantly increased in the spine during osteoarthritis pain. Thus, in contrast to inflammatory pain, the upregulation of spinal COX-1 may be important in osteoarthritis pain.

• MeSH
• artróza kolenních kloubů chemicky indukované   enzymologie   genetika   MeSH
• bolest chemicky indukované   enzymologie   genetika   MeSH
• časové faktory MeSH
• cyklooxygenasa 1 biosyntéza   genetika   MeSH
• cyklooxygenasa 2 biosyntéza   genetika   MeSH
• enzymová indukce MeSH
• hyperalgezie chemicky indukované   enzymologie   genetika   MeSH
• krysa rodu Rattus MeSH
• kyselina jodoctová MeSH
• membránové proteiny biosyntéza   genetika   MeSH
• měření bolesti MeSH
• messenger RNA metabolismus   MeSH
• mícha enzymologie   MeSH
• modely nemocí na zvířatech MeSH
• potkani Wistar MeSH
• práh bolesti MeSH
• reakční čas MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• cyklooxygenasa 1 MeSH
• cyklooxygenasa 2 MeSH
• kyselina jodoctová MeSH
• membránové proteiny MeSH
• messenger RNA MeSH
• Ptgs1 protein, rat MeSH Prohlížeč
• Ptgs2 protein, rat MeSH Prohlížeč