Search

O objetivo do projeto de extensão “INFOCOVID” foi informar a população e profissionais de saúde através de dados científicos, utilizando uma linguagem acessível em diversas estratégias de alcance. Trata-se de um relato de experiência de ações de extensão mediadas por recursos virtuais e equipamentos eletrônicos, mantendo as recomendações de distanciamento social. O projeto foi divulgado no Instagram efetuando “posts, stories e lives” com diferentes conteúdos relacionados ao COVID-19. Considera-se que o projeto tem promovido a responsabilidade social de acadêmicos com a comunidade através da educação em saúde, reinventando meios de alcance e comunicação, com o propósito de promover o bem-estar e a saúde.

The characteristic impairments of the Autism Spectrum Disorder (ASD) may lead children to present limitations in their development, maintenance, and understanding of socio-affective relationships. Therefore, this study investigated the difficulties reported by mothers and fathers in the relationship with their children at risk of ASD or diagnosed with ASD. The participants were eight mothers and eight parents of children at risk of ASD or diagnosed with ASD by means of responding to a semi-structured interview script. From the parents’ report, it was possible to identify that, for most of them, the main difficulty in the relationship with their children was due to the impairments in interactive communication present in the children with risk/diagnosis of ASD. Besides, the parent-child bond built through daily care activities or through playful activities allows the occurrence of behaviors sometimes compromised in ASD. Thus, it is necessary to invest in the bonds with children at risk or diagnosis of this disorder, since they are responsible for the development of compromised aspects of ASD, such as shared attention responsible for the development of interactive communication. Keywords: Autism Spectrum Disorder, mother-child relationship, father- child relationship.

summary Tuberculosis (TB) is a serious public health problem. Development of experimental models and vaccines are essential to elucidate physiopathological mechanisms and to control the disease. Vascular endothelial growth factor (VEGF) is a potent activator of vascular permeability and angiogenesis. VEGF seems to participate in breakdown of the blood brain-barrier (BBB) in tuberculous meningitis (TBM), contributing to worsening of disease. Therefore, the objective here was to extent the characterization of our previously described murine model of central nervous system TB (CNS-TB) by describing the VEGF participation in the CNS disease, and suggesting a vaccination plan in mice. Plasmid encoding DNA protein antigen DNAhsp65 has been described as a protector against TB infection and was used here to test its effectiveness in the prevention of VEGF production and TB disease. Vaccinated mice and its controls were injected with Mycobacterium bovis bacillus Calmette-Guerin (BCG) in cerebellum. Four weeks after BCG injection, mice were perfused and brains were paraffin-embedded for VEGF expression analysis. We observed VEGF immunohistochemical expression in TBM and granulomas in non-vaccinated mice. The DNA-hsp65 treatment blocked the expression of VEGF in mice TBM. Therefore, our murine model indicated the VEGF participation in the physiopathology of CNS-TB and the potential prevention of the DNA-hsp65 in the disease progression.

Central nervous system (CNS) tuberculosis (TB) is the most severe form of TB, characterized morphologically by brain granulomas and tuberculous meningitis (TBM). Experimental strategies for the study of the host-pathogen interaction through the analysis of granulomas and its intrinsic molecular mechanisms could provide new insights into the neuropathology of TB. To verify whether cerebellar mycobacterial infection induces the main features of the disease in human CNS and better understand the physiological mechanisms underlying the disease, we injected bacillus Calmette-Guerin (BCG) into the mouse cerebellum. BCG-induced CNS-TB is characterized by the formation of granulomas and TBM, a build up of bacterial loads in these lesions, and microglial recruitment into the lesion sites. In addition, there is an enhanced expression of signaling molecules such as nuclear factor-κB (NF-κB) and there is a presence of inducible nitric oxide synthase (iNOS) in the lesions and surrounding areas. This murine model of cerebellar CNS-TB was characterized by cellular and biochemical immune responses typically found in the human disease. This model could expand our knowledge about granulomas in TB infection of the cerebellum, and help characterize the physiological mechanisms involved with the progression of this serious illness that is responsible for killing millions people every year.

We have recently demonstrated that gonadal steroid hormones decrease formalin-induced temporomandibular joint nociception in rats. Given that the attenuation of inflammation is a potential mechanism underlying this antinociceptive effect, we evaluated the effect of gonadal steroid hormones on formalin-induced temporomandibular joint inflammation. Plasma extravasation, a major sign of acute inflammation, and neutrophil migration, an important event related to tissue injury, were evaluated. Formalin induced significantly lower temporomandibular joint plasma extravasation and neutrophil migration in proestrus females than in males and in diestrus females. Since estradiol serum level is high in proestrus females and low in diestrus females and in males, these findings suggest that the high physiological level of estradiol decreases temporomandibular joint inflammation. Estradiol but not progesterone administration in ovariectomized females significantly decreased formalin-induced plasma extravasation and neutrophil migration, an effect that was blocked by the estrogen receptor antagonist ICI 182780. Plasma extravasation and neutrophil migration were not affected by orchiectomy, but testosterone or estradiol administration in orchidectomized males significantly decreased them. The androgen receptor antagonist flutamide blocked the anti-inflammatory effect of testosterone while ICI 182780 blocked that of estradiol in males. Previous intravenous administration of a nonspecific selectin inhibitor significantly decreased formalin-induced temporomandibular joint nociception and neutrophil migration in males, revealing a potent and positive correlation between temporomandibular joint nociception and inflammation. Taken together, these findings demonstrate a pronounced anti-inflammatory effect of estradiol and testosterone in the temporomandibular joint region and suggest that this effect may mediate, at least in part, the antinociceptive effect of these hormones.

Activation of peripheral P2X3 and P2X2/3 receptors by endogenous ATP is essential to the development of inflammatory hyperalgesia. We have previously demonstrated that this essential role of P2X3 and P2X2/3 receptors in the development of mechanical hyperalgesia induced by the inflammatory agent carrageenan is mediated by an indirect sensitization of the primary afferent nociceptors dependent on the previous release of tumor necrosis factor alpha (TNF-α) and by a direct sensitization of the primary afferent nociceptors. Therefore, in this study we asked whether activation of P2X3 and P2X2/3 receptors contribute to the mechanical hyperalgesia induced by the inflammatory mediators involved in carrageenan-induced mechanical hyperalgesia, such as bradykinin, tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β), interleukin-6 (IL-6), chemokine-induced chemoattractant-1 (CINC-1), prostaglandin E₂ (PGE₂) and dopamine. Co-administration of the non-selective P2X3 receptor antagonist TNP-ATP or the selective P2X3 and P2X2/3 receptor antagonist A-317491 with bradykinin, but not with TNF-α, IL-1β, IL-6, CINC-1, PGE₂ or dopamine, prevented in a dose-dependent manner the mechanical hyperalgesia. We also verified whether the activation of P2X3 and P2X2/3 receptors by endogenous ATP contributes to bradykinin-induced mechanical hyperalgesia via neutrophil migration and/or cytokine release. Co-administration of TNP-ATP or A-317491 did not affect either neutrophil migration or the increased concentration of TNF-α, IL-1β, IL-6 and CINC-1 induced by bradykinin. These findings demonstrate that the activation of P2X3 and P2X2/3 receptors by endogenous ATP mediates bradykinin-induced mechanical hyperalgesia by a mechanism that does not depend on neutrophil migration or cytokines release.

The aim of this study was to improve the mustard oil (MO) induced temporomandibular joint (TMJ) nociception model and to investigate the potential analgesic activity of systemic dipyrone and tramadol on the nociceptive behavioral responses induced by injection of low concentrations of the MO into the rat TMJ region. TMJ injection of 2.5% MO produced a significant nociceptive behavior expressed by head flinching and orofacial rubbing. This activity was related to the MO injection since mineral oil (vehicle) did not elicit response. Local application of the lidocaine N-ethyl bromide quaternary salt, QX-314 (2%) and systemic administration of morphine (4 mg/kg) significantly reduced the MO-induced nociceptive responses, validating the nociceptive character of the behaviors. The pretreatment with systemic dipyrone (19, 57 or 95 mg/kg) as well as tramadol (5, 7.5 or 10 mg/kg) was effective in decreasing the nociceptive behavioral responses induced by the injection of MO into the rat TMJ. In conclusion, TMJ injection of low concentrations of MO in rats produces well defined and quantifiable nociceptive behaviors constituting a reliable behavioral model for studying TMJ pain mechanisms and testing analgesic drugs. The results also suggest that dipyrone and tramadol could be effective analgesic options in the management of TMJ pain.

We have recently demonstrated that s.c.-injected 5-hydroxytryptamine (5-HT) induces nociception by an indirect action on the primary afferent nociceptor in addition to its previously described direct action. Although the mechanisms mediating hyperalgesia can be quite separate and distinct from those mediating nociception, the aim of this study was to test the hypothesis that 5-HT induces mechanical hyperalgesia by mechanisms similar to those mediating nociception. s.c. injection of 5-HT induced a dose-dependent mechanical hyperalgesia measured by the mechanical paw withdrawal nociceptive threshold test in the rat. 5-HT-induced hyperalgesia was significantly reduced by local blockade of the 5-HT(3) receptor by tropisetron, by the nonspecific selectin inhibitor fucoidan, by the cyclooxygenase inhibitor indomethacin, by guanethidine depletion of norepinephrine in the sympathetic terminals, and by local blockade of the beta(1)- or beta(2)-adrenergic receptor by atenolol or ICI 118,551, respectively. Taken together, these findings indicate that like nociception, hyperalgesia induced by the injection of 5-HT in the s.c. tissue is also mediated by an indirect action of 5-HT on the primary afferent nociceptor. This indirect hyperalgesic action of 5-HT is mediated by a combination of mechanisms involved in inflammation such as neutrophil migration and the local release of prostaglandin and norepinephrine. However, in contrast to nociception, hyperalgesia induced by 5-HT in the s.c. tissue is mediated by a norepinephrine-dependent mechanism that involves the activation of peripheral beta(2) adrenoceptors.

Renin-angiotensin (Ang) system (RAS) peptides injected into the periaqueductal gray matter (PAG) elicit antinociception. Saralasin blocks Ang II-elicited antinociception. Thus, it is possible that endogenous RAS peptides could participate on the modulation of nociception in the PAG. This possibility was tested here injecting, in the PAG, the specific Ang type 1 and type 2 receptor (AT1 receptor and AT(2 receptor) antagonists losartan and CGP42,112A, respectively, either alone or before Ang II. The effects of Ang II, losartan and CGP42,112A on nociception were measured using the tail flick test and the model of incision allodynia. Ang II increased tail-flick latency, an effect inhibited by both losartan and CGP42,112A. Ang II reduced incisional allodynia. Either losartan or CGP42,112A alone increased incision allodynia, suggesting that endogenous Ang II and/or an Ang-peptide participates in the control of allodynia by the PAG. AT1 and AT2 receptors were immunolocalized in neuronal cell bodies and processes in the ventrolateral PAG. Taken together, the antinociceptive effect of Ang II injection into the ventrolateral PAG, the increase of allodynia elicited by injecting either losartan or CGP42,112A alone in the PAG, and the presence of AT1 and AT2 receptors in neurons and neuronal processes in the same region, represent the first evidence that part of the tonic nociceptive control mediated by the PAG is carried out locally by endogenous Ang II and/or an Ang-peptide acting on AT1 and AT2 receptors.

The intracerebroventricular administration of renin substrate or angiotensin II evokes antinociception in rodents, but the brain sites where most of the renin–angiotensin system peptides act are not yet known. This study describes the antinociceptive effects of microinjecting porcine renin substrate tetradecapeptide (RS) or angiotensins I (AI), II (AII) or III (AIII) into different regions of the periaqueductal gray matter (PAG), using the rat tail flick test. All the above peptides were effective following administration into several PAG regions. Their antinociceptive effects were strongly evoked from the caudal ventrolateral and ventral PAG, including the dorsal raphe nucleus. A dose-dependent antinociception following administration into the ventrolateral PAG was demonstrated for all peptides studied. The effect of AII from the ventrolateral PAG was inhibited by the previous local administration of saralasin, a non-selective angiotensin receptor antagonist. Moreover, the peak effects of RS and AI occurred later than those of AII and AIII. The time-course of antinociception suggests that longer-chain peptides are locally processed to biologically active smaller-chain peptides. This study shows for the first time the antinociceptive effect of RS, AI, AII and III in well-defined PAG regions, an effect that is receptor mediated for AII.

We describe here a gradient HPLC procedure for the separation, and quantification by UV absorption of renin tri- and tetradecapeptide substrates, angiotensins I, II, III, IV and V, angiotensin-derived peptides, and peptidase inhibitors including amastatin, bestatin, pepstatin, lisinopril, a renin peptide inhibitor, Z -Pro-prolinal, N -[1-( R , S )-carboxy-2-phenylethyl]- l -Ala- l -Ala- l -Phe- p -aminobenzoate, and phosphoramidon. Most peptides and peptidase inhibitors were baseline-resolved within 32 min. The overall intra- and inter-assay precisions ranged from 0.8 to 5.9 ( n =6) and 2 to 13% ( n =6), respectively. There was a linear relationship (correlation coefficients≥0.9660) between peak height and peptide amount injected. In conclusion, the present method when combined with a peptidase-inhibitor paradigm can lead to the identification of renin–angiotensin system metabolizing enzymes, and when combined with radioimmunoassay can enhance the specificity of angiotensin measurement.

Angiotensins (Angs) modulate blood pressure, hydro-electrolyte composition, and antinociception. Although Ang (5-8) has generally been considered to be inactive, we show here that Ang (5-8) was the smallest Ang to elicit dose-dependent responses and receptor-mediated antinociception in the rat ventrolateral periaqueductal gray matter (vlPAG). Ang (5-8) antinociception seems to be selective, because it did not alter blood pressure or act on vascular or intestinal smooth muscle cells. The non-selective Ang-receptor (Ang-R) antagonist saralasin blocked Ang (5-8) antinociception, but selective antagonists of Ang-R types I, II, IV, and Mas did not, suggesting that Ang (5-8) may act via an unknown receptor. Endopeptidase EP 24.11 and amastatin-sensitive aminopeptidase from the vlPAG catalyzed the synthesis (from Ang II or Ang III) and inactivation of Ang (5-8), respectively. Selective inhibitors of neuronal-nitric oxide (NO) synthase, soluble guanylyl cyclase (sGC) and a non-selective opioid receptor (opioid-R) inhibitor blocked Ang (5-8)-induced antinociception. In conclusion, Ang (5-8) is a new member of the Ang family that selectively and strongly modulates antinociception via NO-sGC and endogenous opioid in the vlPAG.

Activation of peripheral P2X3 and P2X2/3 receptors by endogenous ATP is essential to the development of inflammatory hyperalgesia. We have previously demonstrated that this essential role of P2X3 and P2X2/3 receptors in the development of mechanical hyperalgesia induced by the inflammatory agent carrageenan is mediated by an indirect sensitization of the primary afferent nociceptors dependent on the previous release of tumor necrosis factor alpha (TNF-α) and by a direct sensitization of the primary afferent nociceptors. Therefore, in this study we asked whether activation of P2X3 and P2X2/3 receptors contribute to the mechanical hyperalgesia induced by the inflammatory mediators involved in carrageenan-induced mechanical hyperalgesia, such as bradykinin, tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β), interleukin-6 (IL-6), chemokine-induced chemoattractant-1 (CINC-1), prostaglandin E₂ (PGE₂) and dopamine. Co-administration of the non-selective P2X3 receptor antagonist TNP-ATP or the selective P2X3 and P2X2/3 receptor antagonist A-317491 with bradykinin, but not with TNF-α, IL-1β, IL-6, CINC-1, PGE₂ or dopamine, prevented in a dose-dependent manner the mechanical hyperalgesia. We also verified whether the activation of P2X3 and P2X2/3 receptors by endogenous ATP contributes to bradykinin-induced mechanical hyperalgesia via neutrophil migration and/or cytokine release. Co-administration of TNP-ATP or A-317491 did not affect either neutrophil migration or the increased concentration of TNF-α, IL-1β, IL-6 and CINC-1 induced by bradykinin. These findings demonstrate that the activation of P2X3 and P2X2/3 receptors by endogenous ATP mediates bradykinin-induced mechanical hyperalgesia by a mechanism that does not depend on neutrophil migration or cytokines release.

The aim of this study was to investigate the role of P2X3, P2X2/3 and P2X7 receptors in the development of TMJ hyperalgesia induced by carrageenan. We also investigated the expression of mRNA of P2X7 receptors in the trigeminal ganglia and the existence of functional P2X7 receptors in the rat's TMJ. The P2X1, P2X3 and P2X2/3 receptor antagonist TNP-ATP, but not the selective P2X7 receptor antagonist A-438079, significantly reduced carrageenan-induced TMJ inflammatory hyperalgesia. The qPCR assay showed that mRNA of P2X7 receptors are expressed in the trigeminal ganglia but this expression is not increased by the inflammation induced by carrageenan in the TMJ region. The P2X7 receptor agonist BzATP induced TMJ inflammatory hyperalgesia that was significantly reduced by pretreatment with dexamethasone. These results indicate that P2X3 and P2X2/3 but not P2X7 receptors are involved in carrageenan-induced TMJ inflammatory hyperalgesia. However, functional P2X7 receptors are expressed in the TMJ region. The activation of these receptors by BzATP sensitizes the primary afferent nociceptors in the TMJ through the previous release of inflammatory mediators. The findings of this study point out P2X3 and P2X2/3 receptors, but not P2X7 receptors, as potential targets for the development of new analgesic drugs to control TMJ inflammatory pain.

Endogenous angiotensin (Ang) II and/or an Ang II-derived peptide, acting on Ang type 1 (AT(1)) and Ang type 2 (AT(2)) receptors, can carry out part of the nociceptive control modulated by periaqueductal gray matter (PAG). However, neither the identity of this putative Ang-peptide, nor its relationship to Ang II antinociceptive activity was clarified. Therefore, we have used tail-flick and incision allodynia models combined with an HPLC time course of Ang metabolism, to study the Ang III antinociceptive effect in the rat ventrolateral (vl) PAG using peptidase inhibitors and receptor antagonists. Ang III injection into the vlPAG increased tail-flick latency, which was fully blocked by Losartan and CGP 42,112A, but not by divalinal-Ang IV, indicating that Ang III effect was mediated by AT(1) and AT(2) receptors, but not by the AT(4) receptor. Ang III injected into the vlPAG reduced incision allodynia. Incubation of Ang II with punches of vlPAG homogenate formed Ang III, Ang (1-7) and Ang IV. Amastatin (AM) inhibited the formation of Ang III from Ang II by homogenate, and blocked the antinociceptive activity of Ang II injection into vlPAG, suggesting that aminopeptidase A (APA) formed Ang III from Ang II. Ang III can also be formed from Ang I by a vlPAG alternative pathway. Therefore, the present work shows, for the first time, that: (i) Ang III, acting on AT(1) and AT(2) receptors, can elicit vlPAG-mediated antinociception, (ii) the conversion of Ang II to Ang III in the vlPAG is required to elicit antinociception, and (iii) the antinociceptive activity of endogenous Ang II in vlPAG can be ascribed preponderantly to Ang III.

Aims The aim of this study was to investigate whether the injection of nerve growth factor induces spontaneous nociceptive behavior in the intact or sensitized temporomandibular joint (TMJ) of rats. Main methods NGF was injected into the TMJ 1 h after the TMJ injection of saline or carrageenan and the spontaneous nociceptive behavior was quantified. The mechanism involved in this phenomenon was investigated by the injection of NGF into the carrageenan-sensitized TMJ in the presence of indomethacin or of β-adrenergic antagonists. Key findings NGF injected into the TMJ sensitized by a prior TMJ injection of carrageenan but not into the intact TMJ induced a significant nociceptive behavior. Co-injection of the non-specific Trk receptor antagonist k252A with NGF 1 h after the TMJ injection of carrageenan significantly reduced NGF-induced spontaneous nociception supporting the Trk receptor activation in this nociceptive effect. Blockade of prostaglandin synthesis by indomethacin before the TMJ injection of carrageenan did not reduce NGF-induced nociception. Co-administration of carrageenan with the β2-adrenoceptor antagonist ICI 118.55 but not with the β1-adrenoceptor antagonist atenolol significantly reduced NGF-induced nociception. The injection of NGF the TMJ sensitized by a previous TMJ injection of epinephrine also induced nociceptive behavior. Significance Taken together, these results indicate that NGF can induce TMJ nociception during TMJ inflammation. Moreover, the expression of this nociceptive response seems to depend on the synergic activity of NGF and sympathetic amines released during TMJ inflammation acting on β2-adrenergic receptors.

Activation of P2X3,2/3 receptors by endogenous ATP contributes to the development of inflammatory hyperalgesia. Given the clinical importance of mechanical hyperalgesia in inflammatory states, we hypothesized that the activation of P2X3,2/3 receptors by endogenous ATP contributes to carrageenan-induced mechanical hyperalgesia and that this contribution is mediated by an indirect and/or a direct sensitization of the primary afferent nociceptors. Co-administration of the selective P2X3,2/3 receptors antagonist A-317491, or the non-selective P2X3 receptor antagonist, TNP-ATP, with carrageenan blocked the mechanical hyperalgesia induced by carrageenan, and significantly reduced the increased concentration of tumor necrosis factor alpha (TNF-alpha) and chemokine-induced chemoattractant-1 (CINC-1) but not of interleukin-1 beta (IL-1 beta) induced by carrageenan. Co-administration of the selective P2X3,2/3 receptors antagonist A-317491 with carrageenan did not affect the neutrophil migration induced by carrageenan. Intrathecal administration of oligonucleotides antisense against P2X3 receptors for seven days significantly reduced the expression of P2X3 receptors in the saphenous nerve and significantly reduced the mechanical hyperalgesia induced by carrageenan. We concluded that the activation of P2X3,2/3 receptors by endogenous ATP is essential to the development of the mechanical hyperalgesia induced by carrageenan. Furthermore, we showed that this essential role of P2X3,2/3 receptors in the development of carrageenan-induced mechanical hyperalgesia is mediated by an indirect sensitization of the primary afferent nociceptors dependent on the previous release of TNF-alpha and by a direct sensitization of the primary afferent nociceptors.

The aim of this study was to test the hypothesis that 5-hydroxytryptamine induces nociception by an indirect action on the primary afferent nociceptor in addition to its previously described direct action. Injection of 5-hydroxytryptamine into the s.c. tissue of the hind paw of rats produced nociceptive flinch behavior and inflammatory cell migration, that were significantly reduced by the nonspecific selectin inhibitor fucoidan. 5-Hydroxytryptamine-induced nociception was also significantly reduced by local blockade of the 5-HT 3 receptor by tropisetron, by the cyclooxygenase inhibitor indomethacin and by local blockade of the β1-adrenergic receptor or of the D1 receptor by atenolol or SCH 23390, respectively. Neither guanethidine depletion of norepinephrine in the sympathetic terminals nor local blockade of the β2-adrenergic receptor by ICI-118,551 significantly reduced 5-hydroxytryptamine-induced nociception. Taken together, these findings indicate that 5-hydroxytryptamine induces nociception by a novel, indirect and norepinephrine-independent mechanism mediated by neutrophil migration and local release of prostaglandin and dopamine. Furthermore, to test whether dopamine acts on β1-adrenergic and/or D1 receptor to contribute to 5-hydroxytryptamine-induced nociception, dopamine was s.c. injected either alone or combined with atenolol or with SCH 23390. S.c.-injected dopamine also produced a dose-dependent nociceptive behavior that was significantly reduced by both SCH 23390 and atenolol. Based on that it is proposed that dopamine, once released, activates D1 and β1-adrenergic receptors to contribute to 5-hydroxytryptamine-induced nociception.

The aim of this study was to further validate our carrageenan-induced temporomandibular joint (TMJ) inflammatory hyperalgesia model in rats by showing that administration of indomethacin before the initiation of inflammation would diminish the TMJ hyperalgesia. Using this model, we investigated whether norepinephrine and local β-adrenoceptors contribute to the development of inflammatory TMJ hyperalgesia. Carrageenan-induced TMJ hyperalgesia was assessed by measuring the behavioral nociceptive responses, such as rubbing the orofacial region and flinching the head, induced by the injection of a low dose of 5-hydroxytryptamine into the TMJ sensitized 1 h before by a TMJ injection of carrageenan. Blockade of prostaglandin synthesis by indomethacin prior to initiation of inflammation by carrageenan significantly attenuated the TMJ hyperalgesia. The guanethidine depletion of norepinephrine or the blockade of β 2 but not the blockade of the β 1 - adrenoceptor by the selective adrenoceptor antagonists ICI 118.55 and atenolol, respectively, significantly reduced carrageenan-induced TMJ hyperalgesia. In the present study, we further validated our carrageenan-induced TMJ hyperalgesia model to study the mechanisms involved in inflammatory TMJ hyperalgesia and to test the analgesic effect of different types of peripheral analgesics. We also demonstrated that norepinephrine released at the site of injury contributes to the development of the inflammatory TMJ hyperalgesia by the activation of β 2 -adrenoceptors. Perspective The findings that local sympathomimetic amines contribute to the inflammatory TMJ hyperalgesia by activating β 2 -adrenoceptors may be relevant to clinical TMJ inflammatory pain states less sensitive to nonsteroidal anti-inflammatory drugs.