Infusion of Gabrα6 siRNA into the trigeminal ganglia increased the myogenic orofacial nociceptive response of ovariectomized rats treated with 17ß-estradiol.

High levels of 17ß-estradiol (E2) have been found to reduce inflammatory temporomandibular joint (TMJ) pain. A search for genes effected by a high concentration of estradiol showed an increase in GABAA receptor subunit alpha 6 (Gabrα6) in the trigeminal ganglia (TG). Blockade of Gabrα6 expression in the TG increases masseter muscle nociception in male rats, but the relationship between estradiol's effect on nociception and Gabrα6 expression remains unclear in females. To address this knowledge gap we hypothesized that reducing Gabrα6 expression in the TG will increase the orofacial nociceptive response of ovariectomized female rats treated with estradiol. To administer hormone osmotic pumps were placed in rats that dispensed a low diestrus plasma concentration of 17ß-estradiol, in addition, 17ß-estradiol was injected to produce a high proestrus plasma concentration of estradiol. A ligature was then placed around the masseter tendon to induce a nociceptive response; a model for TMJ muscle pain. Gabrα6 small interfering RNA (siRNA) was later infused into the TG and the nociceptive response was measured using von Frey filaments and a meal duration assay. GABAA receptor expression was measured in the TG and trigeminal nucleus caudalis and upper cervical region (Vc-C1). Ligature significantly increased the nociceptive response but a high proestrus concentration of 17ß-estradiol attenuated this response. Gabrα6 siRNA infusion decreased Gabrα6 expression in the TG and Vc-C1 but increased the nociceptive response after 17ß-estradiol treatment. The results suggest estradiol decreased the orofacial nociceptive response, in part, by causing an increase in Gabrα6 expression.

Reduced GABAA receptor α6 expression in the trigeminal ganglion enhanced myofascial nociceptive response.

Activation of the GABAA receptor results in inhibition of neuronal activity. One subunit of this multi-subunit receptor termed alpha 6 (Gabrα6) contributed to inflammatory temporomandibular joint (TMJ) nociception but TMJ disorders often include myofascial pain. To address Gabrα6 role in myofascial pain we hypothesized that Gabrα6 has an inhibitory role in myofascial nociceptive responses similar to inflammatory TMJ arthritis. To test this hypothesis a, myofascial nociceptive response was induced by placing a ligature bilaterally on the tendon attachment of the anterior superficial part of a male rat's masseter muscle. Four days after ligature placement Gabrα6 expression was reduced by infusing the trigeminal ganglia (TG) with small interfering RNA (siRNA) having homology to either the Gabrα6 gene (Gabrα6 siRNA) or no known gene (control siRNA). After siRNA infusion nociceptive behavioral responses were measured, i.e., feeding behavior and head withdrawal after pressing upon the region above the ligature with von Frey filaments. Neuronal activity in the TG and trigeminal nucleus caudalis and upper cervical region (Vc-C1) was measured by quantitating the amount of phosphorylated extracellular signal-regulated kinase (p-ERK). Total Gabrα6 and GABAA receptor contents in the TG and Vc-C1 were determined. Gabrα6 siRNA infusion reduced Gabrα6 and GABAA receptor expression and significantly increased the nociceptive response in both nociceptive assays. Gabrα6 siRNA infusion also significantly increased TG p-ERK expression of the ligated rats. From these results we conclude GABAA receptors consisting of the Gabrα6 subunit inhibit TG nociceptive sensory afferents in the trigeminal pathway and have an important role in the regulation of myofascial nociception.

Modulation of temporomandibular joint nociception and inflammation in male rats after administering a physiological concentration of 17ß-oestradiol.

BACKGROUND: Previous studies have shown 17ß-estradiol will reduce temporomandibular joint (TMJ) inflammation and hypersensitivity in female rats. Although male rats contain significant amounts of oestradiol, it was unknown whether a physiological concentration of 17ß-estradiol would attenuate male TMJ inflammation and nociception. METHODS: Intact and castrated rats were given a physiological concentration of oestradiol to examine first, if oestradiol will affect male TMJ nociception/inflammation and, second, if administration of oestradiol would act synergistically with endogenous male hormones to attenuate TMJ nociception. The hormonally treated rats were given TMJ injections of complete Freund's adjuvant (CFA) and then nociception was measured using a validated method in which a lengthening in meal duration is directly correlated to the intensity of deep TMJ nociception. Inflammation was assayed by quantitating pro-inflammatory gene expression. RESULTS: Meal duration was significantly lengthened after TMJ CFA injection and this lengthening was significantly attenuated in the castrated but not intact males after administering a physiological concentration of oestradiol. A physiological concentration of 17ß-estradiol also significantly increased IL-6 expression in the inflamed TMJ of castrated males while 17ß-estradiol did not alter IL-1ß, CXCL2 and CCL20 expression. Castration increased pro-inflammatory mediators IL-6, IL-1ß and CXCL2 suggesting male sex hormones were anti-inflammatory. Calcitonin gene-related peptide in the trigeminal ganglia was unchanged. CONCLUSIONS: Similar to females, male rats with TMJ inflammation showed a reduced nociceptive response after treatment with a physiological concentration of oestradiol suggesting the effects of oestradiol treatment were not constrained by organizational processes in the males.

A non-invasive model for measuring nociception after tooth pulp exposure.

Temporomandibular arthritis will lengthen a rodent's meal duration. We hypothesized that meal duration would also lengthen after tooth pulp exposure, suggesting that this behavior could be used to measure tooth nociception. To test this hypothesis, we placed rats in feeding units and subjected 4 anterior mandibular molars to pulp exposure, with and without pre-treatment with the analgesic buprenorphine-HCl. In the first study, male Sprague-Dawley rats were placed in computerized sound-attenuated feeding modules, the pulp of 4 molars on the mandible were exposed, and meal duration was measured for 13 days. In a second study, rats were injected with either the analgesic buprenorphine-HCl or saline every 12 hrs; injections were started one day before pulp exposure. Meal duration was determined before and after treatment. In the first study, pulp exposure significantly increased daily meal duration for 8 days. In the second study, pulp exposure lengthened daily meal duration, but the group that was treated with buprenorphine-HCl showed no significant difference compared with control rats without pulp exposure. Evidence supports that a lengthening in meal duration is a response to tooth nociception and that this nociception can be measured for over a week.

Reduced GABA(A) receptor α6 expression in the trigeminal ganglion alters inflammatory TMJ hypersensitivity.

Trigeminal ganglia neurons express the GABA(A) receptor subunit alpha 6 (Gabrα6) but the role of this particular subunit in orofacial hypersensitivity is unknown. In this report the function of Gabrα6 was tested by reducing its expression in the trigeminal ganglia and measuring the effect of this reduction on inflammatory temporomandibular joint (TMJ) hypersensitivity. Gabrα6 expression was reduced by infusing the trigeminal ganglia of male Sprague Dawley rats with small interfering RNA (siRNA) having homology to either the Gabrα6 gene (Gabrα6 siRNA) or no known gene (control siRNA). Sixty hours after siRNA infusion the rats received a bilateral TMJ injection of complete Freund's adjuvant to induce an inflammatory response. Hypersensitivity was then quantitated by measuring meal duration, which lengthens when hypersensitivity increases. Neuronal activity in the trigeminal ganglia was also measured by quantitating the amount of phosphorylated ERK. Rats in a different group that did not have TMJ inflammation had an electrode placed in the spinal cord at the level of C1 sixty hours after siRNA infusion to record extracellular electrical activity of neurons that responded to TMJ stimulation. Our results show that Gabrα6 was expressed in both neurons and satellite glia of the trigeminal ganglia and that Gabrα6 positive neurons within the trigeminal ganglia have afferents in the TMJ. Gabrα6 siRNA infusion reduced Gabrα6 gene expression by 30% and significantly lengthened meal duration in rats with TMJ inflammation. Gabrα6 siRNA infusion also significantly increased p-ERK expression in the trigeminal ganglia of rats with TMJ inflammation and increased electrical activity in the spinal cord of rats without TMJ inflammation. These results suggest that maintaining Gabrα6 expression was necessary to inhibit primary sensory afferents in the trigeminal pathway and reduce inflammatory orofacial nociception.

[Value of the functional neural tractography in the reconstruction of the visual pathways in DTMRI]. / Intérêt de la neurotractographie fonctionnelle dans la reconstruction des voies visuelles en IRMTD.

OBJECTIVE: This article shows that functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) are very useful in the in vivo description of the visual pathways using today's most advanced techniques and allowing fusion between fMRI and tractography. Two complementary techniques were combined: (1) DTI coupled with the tractography and (2) fMRI. MATERIALS AND METHODS: A group of 205 cases, normal and pathological, children and adults, were studied for tractographic reconstitution of visual pathways. In addition, 11 patients underwent an acquisition in fMRI (BOLD effect), with a stimulation of a black-and-white flickering checkerboard. Acquisition was carried out on a 3.0 Tesla GEHC MRI unit. Activated arrays of fMRI are overlaid with those of neurotractography (neural tractography) having like results a functional neurotractography. RESULTS AND DISCUSSION: The main components of the visual pathways were successfully reconstructed in tractography: the optic nerves, optic chiasm, optic tracts, and optic radiations. It was also possible to visualize fiber decussation within the chiasma (possible direct pathways to the hypothalamus and thalamus were also identified). CONCLUSIONS: The tensor of diffusion is increasingly used and is a promising technology to improve the diagnosis of neurological diseases. Sophisticated algorithms contribute a new vision of the anatomy, with the possibility of isolating distinct anatomical entities. With the software used, the charts of fMRI activation are overlaid on the anisotropy charts. The tractograms that link two regions of the same functional network thus provide information on subjacent structural connectivity. Consequently, one speaks about functional neurotractography.

The effects of chronic nicotine on meal patterns, food intake, metabolism and body weight of male rats.

It is unclear what contribution food intake and metabolism have in causing weight loss after administering a dose of nicotine equivalent to smoking one to three packs of cigarettes per day because previous studies have been of a very short duration. To address this question, male Sprague Dawley rats were housed in computerized food intake modules and fed 45 mg pellets: Group 1 [nicotine injected with 1.4 mg/kg/day (free base), fed ad libitum]; and Group 2 [saline injected and pair-fed by computer with Group 2]; and Group 3 [saline injected (i.p.), fed ad libitum]. The rats received 4 equally spaced injections over the dark phase. Treatment consisted of: Phase 1 (nicotine or saline for 14 days), Phase 2 (all rats saline for 8 days and Phase 3 (pair-fed group "unyoked" for 6 days)). Nicotine inhibited food intake over the first 6 days. On termination of nicotine, there was no compensatory hyperphagia in either Groups 1 or 2; and their body weight was reduced starting on day 5 until day 28. In another study, rats were housed in an indirect calorimetry system. Saline or nicotine was injected for 14 days, as noted above; then all rats were injected with saline for 4 days and then no injections for 10 days to follow changes in body weight. Energy expenditure (Kcal/Kg(0.75)) was measured for 18 days. Nicotine significantly reduced food intake on 7 of 14 days of nicotine injections. The body weight of the nicotine injected rats was significantly reduced starting on day 3 until day 25. There were no differences in energy expenditures of the groups, which suggested that a decrease in food intake and not an increase in metabolism was the reason the rats lost weight after administering nicotine.

The effects of cycling levels of 17beta-estradiol and progesterone on the magnitude of temporomandibular joint-induced nociception.

A greater incidence of temporomandibular joint (TMJ) pain is reported in females, suggesting that gonadal hormones may play a role in this condition. However, the exact roles of 17beta-estradiol (E2) and progesterone (P4) in TMJ pain are not completely known. Two experiments were performed to determine the separate roles of E2 and P4 in TMJ nociception at various stages of the estrous cycle. Ovariectomized (OVX) rats were cycled with physiological concentrations of E2 or P4. The E2-cycled rats then received bilateral TMJ injections of saline (SAL) or complete Freund's adjuvant (CFA) on the morning of diestrus-2 (low E2 condition) or proestrus (high E2 condition). As a control, OVX rats (no ovarian E2 and no replacement) were injected with SAL or CFA. The TMJ nociception was measured using a validated novel method in which an increase in meal duration directly correlated to the intensity of deep TMJ nociception. In the E2 experiment, CFA injection, but not SAL, increased TMJ nociception in the OVX group, but the effect was less pronounced in diestrus-2 and even less in proestrus. In the P4 experiment, the rats receiving TMJ CFA in diestrus-2 (end of minor P4 surge) did not show an increase in TMJ nociception, whereas the rats injected in proestrus (major P4 surge), estrus (low P4), and metestrus (low P4) had similar increases in TMJ nociception. The hormones' concentration did not affect TMJ IL-1beta, IL-6, C-C motif ligand 20, or C-X-C motif ligand 2 or the trigeminal ganglia calcitonin gene-related peptide. The high physiological concentrations of E2 observed at proestrus and the low P4 concentrations observed at diestrus-2 attenuated or eliminated CFA-induced TMJ nociception. The results suggest that the cyclic estrous cycle concentrations of E2 and P4 can influence CFA-induced TMJ nociception in the rat.

Exposure to undernutrition in fetal life determines fat distribution, locomotor activity and food intake in ageing rats.

OBJECTIVE: To assess the long-term impact of undernutrition during specific periods of fetal life, upon central adiposity, control of feeding behaviour and locomotor activity. DESIGN: Pregnant rats were fed a control or low-protein (LP) diet, targeted to early (LPE), mid (LPM) or late (LPL) pregnancy or throughout gestation (LPA). The offspring were studied at 9 and 18 months of age. MEASUREMENTS: Adiposity was assessed by measuring weight of abdominal fat depots relative to body weight. Locomotor activity was assessed using an infrared sensor array system in both light and dark conditions. Hypothalamic expression of mRNA for galanin and the galanin 2 receptor (Gal2R) was determined using real-time PCR. RESULTS: At 9 months, male rats exposed to LP in utero had less fat in the gonadal depot, but were of similar body weight to controls. By 18 months, the males of groups LPA and LPM had more abdominal and less subcutaneous fat. Females deposited more fat centrally than males between 9 and 18 months of age, and this was more marked in groups LPA and LPL. Food intake was greater in LPM males. Among females hypophagia was noted in groups LPA and LPL. Expression of galanin and Gal2R were unaffected by maternal diet. Total locomotor activity was reduced in LPE males and all LP females in the light but not in the dark. CONCLUSION: Locomotor activity and feeding behaviour in aged rats are subject to prenatal programming influences. Fetal undernutrition does not programme obesity in rats without postnatal dietary challenge.

[Functional amblyopia: a functional MRI evaluation of the visual cortex response after treatment]. / Amblyopie fonctionnelle : évaluation en IRM fonctionnelle de la réponse corticale visuelle après traitement.

PURPOSE: Functional MRI evaluation of the cortical response in treated amblyopic patients. MATERIAL AND METHODS: Clinical and functional MRI exploration of ten patients, seven men and three women aged from 21 to 59 years, with strabismus management during childhood. Functional evaluations were performed on a 1.5 Tesla MR device, with four monocular functional sessions, two stimulations per eye. Alternating rest and active phases displayed still and flickering black and white checkerboards with spatial and temporal frequencies of 1 degree/8Hz and 15'/4Hz. Anatomical realignment and statistical analysis were performed using SPM99 (Statistical Parametric Mapping) to compare the four sessions in individuals. RESULTS AND DISCUSSION: In patients presenting a visual acuity of the amblyopic eye less than 0.7, stimulation of this eye induced lower response in V1, V3, and V5 in comparison with the contralateral eye stimulation. Unexpectedly, in patients recovering normal or subnormal acuity, the amblyopic eye gave comparable or enhanced response in these areas. Additional response was found in the secondary visual cortex, the cuneus, the lingual gyrus, and in parietal, frontal, and orbitofrontal areas. These results suggest a variation in cortical response depending on the efficacy of the treatment. Recovered amblyopic eye, even with acuity less than the contralateral eye, may induce a reinforced cortical sensitivity to visual stimulus. Secondary visual areas may contribute to an attentional process in image perception and analysis. Cortical plasticity may be observed several years after amblyopia treatment. CONCLUSION: Our study substantiates the importance of an effective and early treatment of functional amblyopia, inducing cortical plasticity with reinforced attention and sensitivity to visual perception.

Specificity of meal pattern analysis as an animal model of determining temporomandibular joint inflammation/pain.

Analyzing feeding behavior, and in particular meal duration, can be used as a biological marker for temporomandibular joint (TMJ) inflammation/pain. The present study determined the specificity of meal duration as a measure of TMJ inflammation/pain in a rodent model. The model was also used to test the efficacy of dexamethasone (DEX) as a treatment for TMJ inflammation/pain that was induced by TMJ injection of complete Freund's adjuvant (CFA). In the first study, anesthetized male Sprague-Dawley rats housed in computerized feeding modules received bilateral intra-articular knee injections of CFA or saline. The next day, CFA-injected rats had significant knee swelling and impaired mobility. Food intake in the CFA-injected group was reduced over the next two days and this was due to reduced meal number with no change in meal size. Notably, meal duration was normal in both the CFA and saline knee-injected groups. In the second study, male rats were assigned to one of four groups: Group 1, no CFA and no DEX treatment; Group 2, no CFA and treatment with DEX (0.4 mg/kg i.m. once daily); Group 3, bilateral TMJ CFA injection and no DEX treatment; and Group 4, bilateral TMJ CFA injection and treatment with DEX. CFA significantly increased TMJ swelling and stress-induced chromodacryorrhea in Group 3, but treatment with DEX attenuated these effects in Group 4. Compared to the controls, meal duration was significantly lengthened 24 and 48 h post-CFA injection in Group 3, whereas DEX treatment attenuated TMJ swelling, chromodacryorrhea and normalized meal duration. The data demonstrate that meal pattern analysis, and in particular meal duration, can be used as a non-invasive specific measure of TMJ inflammation/pain and can be used as a marker of DEX treatment efficacy.

MR tractography with diffusion tensor imaging in clinical routine.

Using MRI, we demonstrated that the depiction of the cerebral white matter fiber tracts has become a routine procedure. Diffusion tensor (DT) sequences may be analyzed with combined volume analysis and tractography extraction software, giving indirect visualization of white matter connections. We obtained DT data from 20 subjects with normal MR imaging and five patients presenting cerebral diseases such as brain tumors, multiple sclerosis and stroke, with five patients explored on two different MR scanners. Data were transferred to dedicated workstations for anatomical realignment, determination of voxel eigenvectors and calculation of fiber tract orientations in a region of interest. In all subjects, axonal directions underlying the main neuronal pathways could be delineated. Comparisons between diseased regions and contralateral areas demonstrated changes in voxel anisotropy in injured regions, revealing possible preferential fiber orientations within diffuse T2 hyperintensities. Rapid data processing allows imaging of the normal and diseased fiber pathways as part of the routine MRI examination. Therefore, it appears that whenever white matter disease is suspected a tractography can be performed with this fast and simple method that we proved to be reliable and reproducible.

[Tractography of the visual pathways: routine examination in magnetic resonance imaging]. / Tractographie des voies visuelles: évaluation en routine en imagerie par résonance magnétique.

Water diffusion analysis in magnetic resonance imaging (MRI) provides an elective visualization of fiber tract orientations in cerebral white matter, especially for optic tracts. We explored 25 patients from 18 to 45 years of age, with normal MRI in 20 subjects, and radiological anomalies in five. On a 1.5 Tesla MRI apparatus, diffusion tensor acquisitions were performed in 5 minutes 58 seconds with an EPI Single Shot sequence covering the entire brain. Image displacements were precluded by patient information and adequate fixation, then digitally corrected on workstations. Volume merging and fiber tract extraction were achieved using dedicated software (Volume-One and dTV). A directional depiction was obtained for all areas in the white matter, in particular for white matter junctions. Coming from the lateral geniculate body, the optic tracts were directed posteriorly toward the occipital cortex, with numerous connections to extrastriate associative areas, and through the corpus callosum and the fornix. Diffusion tractography requires optimization of volume displacements, before and secondary to MRI acquisitions. Our diffusion tensor acquisition, with image optimization in a short-duration sequence can be routinely applied to all patients, for a specific analysis of functional connections between cortical areas of cerebral white matter.

The prospective use of COX-2 inhibitors for the treatment of temporomandibular joint inflammatory disorders.

Development of a new class of drugs designed to selectively inhibit the inducible cyclooxygenase isoenzyme, COX-2, was initially prescribed for individuals diagnosed with osteoarthritis or rheumatoid arthritis. Although these inflammatory disorders are more typically related to the joints of the knee, ankle, or hand, the temporomandibular joint (TMJ) plays a special role due to its involvement in our normal day-to-day activities of eating and communicating. The TMJ, unlike most of the other joints, contains some unique morphological characteristics that support various inflammatory disorders. An overview of these characteristics and the prospective use of the COX-2 inhibitors for temporomandibular joint inflammation are presented.

A determination of tumor necrosis factor expression in TMJ inflammation with the use of microarray analysis.

Many different factors can lead to inflammatory changes within temporomandibular joint tissues. This investigation examined if the expression of TNF-alpha and its receptors was altered in TMJ tissues during inflammation. Adult male rats were injected bilaterally with complete Freund's adjuvant (CFA) into the TMJ or served as uninjected controls and were killed two days after CFA treatment. TMJ tissues were removed, and expression of TNF-alpha and its receptors was examined via gene microarray analysis, RT-PCR, Western blot, and ELISA. Gene microarray analysis provided evidence for changes in gene expression, notably that TNF-alpha and TNF-R1, but not TNF-R2, were significantly elevated in CFA-treated TMJ tissues. However, protein levels of TNF-alpha, TNF-R1, and TNF-R2 were all significantly increased in CFA-treated TMJ tissues. These results indicate that the pro-inflammatory cytokine TNF-alpha may play a significant role in the onset of inflammatory conditions associated with adjuvant-induced arthritis of the TMJ.

Meal pattern changes associated with temporomandibular joint inflammation/pain in rats; analgesic effects.

Establishing a valid animal model to study temporomandibular joint (TMJ) pain has proven extremely difficult. Using complete Freund's adjuvant (CFA) to induce TMJ inflammation, we recently showed that meal pattern analysis could be used as a noninvasive biological marker to study TMJ pain in an animal model. The purpose of this study was to further validate our animal model by determining whether aspects of CFA-induced TMJ inflammation/pain are reversed with ibuprofen (IBU) treatment. In the first trial, 48 male rats were used and in the second trial, 32 female ovariectomized rats, given 17beta-estradiol replacement, were used. The rats were assigned to one of four groups: control (CON-CON); control+IBU (CON+IBU); CFA-CON; and CFA+IBU. In the male trial, CFA injection (P<.01) caused TMJ swelling and chromodacryorrhea (CFA-CON); IBU eliminated these changes in the CFA+IBU group. Meal pattern analysis showed the pertinent CFA-induced change and the IBU effect was that meal duration was increased in the CFA-CON group (P<.01), but normal in the CFA+IBU-treated group on the first, but not second, day postinjection. In the female trial, CFA increased TMJ swelling, but did not cause significant chromodacryorrhea (CFA-CON); IBU eliminated swelling in the CFA+IBU group. Meal duration was increased (P<.01) in the CFA-CON group, but was normal in the CFA+IBU-treated group on both the first and second days postinjection. In both trials, interleukin-1beta (IL-1beta) levels were increased similarly in CFA-CON and CFA+IBU groups (P<.01). This study shows that CFA-induced TMJ inflammation/pain can cause changes in meal patterns (i.e., meal duration), which may be used as a behavioral marker for TMJ inflammation/pain.

Modulation of the inflammatory response in the rat TMJ with increasing doses of complete Freund's adjuvant.

OBJECTIVES: Acute inflammation stresses the physiological system, which must respond in order to reestablish homeostasis. The purpose of this study was to determine whether bilateral temporomandibular joint (TMJ) injections of different doses of Complete Freund's Adjuvant (CFA) produced dose-dependent changes in biologic markers of acute inflammation. The ability to establish an animal model with varying degrees of joint inflammation would allow evaluation of agents or conditions that could modulate the severity of the disease. DESIGN: The TMJs of three groups of male Sprague-Dawley rats were injected with CFA containing varying doses of Mycobacterium tuberculosis (MT). A group of non-injected and a group of saline injected rats were used as controls. Food intake, body weights, swelling and chromodacryorrhea were recorded daily. Interleukin-1 beta (IL-1 beta) and corticosterone levels were assayed and condylar cartilage thickness was measured 48 h after injections. RESULTS: Twenty-four hours post-injection, bilateral TMJ swelling and chromodacryorrhea were significantly (P< 0.05) increased following 10 microg of MT and further increased with elevated MT dose. In the CFA groups food intake was attenuated (P< 0.01) 24 and 48 h post-injection and negatively correlated with dose at 24 h. Body weight was also negatively correlated with dose. TMJ retrodiscal tissues IL-1 beta was increased (P< 0.05) in a dose-dependent manner. CFA increased corticosterone (P< 0.05), but this elevation was not dose dependent. Condylar cartilage thickness was decreased in a dose-dependent manner. CONCLUSIONS: These data suggest that an intermediate dose of CFA can be used to effect submaximal levels of TMJ inflammation that will allow experimental modulation in future studies.

Meal pattern analysis in response to temporomandibular joint inflammation in the rat.

Inflammation of the temporomandibular joint (TMJ) can alter behavioral responses such as food intake and mobilize stress hormones. The hypothesis of this study was that food intake and diurnal corticosterone analysis can be used as indicators of adjuvant-induced TMJ inflammation. Groups of rats received adjuvant or no injections at the beginning of the resting (AM) or activity (PM) phase. Forty-eight hours (early) or 6 weeks (late) after adjuvant injection, plasma corticosterone was assayed and food intake was recorded. Food intake was suppressed up to 4 days post-injection. As expected, the non-injected group showed low AM and high PM corticosterone. AM corticosterone was elevated, but PM corticosterone was attenuated in both early- and late-stage-injected rats. A computerized pair-fed experiment showed that adjuvant-induced hypophagia did not alter corticosterone levels. Meal pattern analysis revealed decreased food intake due to a decrease in the number of meals taken. Notably, meal size remained the same but meal duration increased. This model demonstrated that food intake and stress hormone analysis could be used as indicators for sequelae of adjuvant-induced TMJ inflammation.

Differential effects of selective vagotomy and tropisetron in aminoprivic feeding.

Both total subdiaphragmatic vagotomy (TVAGX) and serotonin(3) receptor blockade with tropisetron or ondansetron attenuate amino acid-imbalanced diet (Imb) anorexia. Total vagotomy is less effective than tropisetron in reducing Imb-induced anorexia and also blunts the tropisetron effect. With the use of electrocautery at the subdiaphragmatic level of the vagus, we severed the ventral and dorsal trunks as well as the hepatic, ventral gastric, dorsal gastric, celiac, and accessory celiac branches separately or in combination to determine which vagal branches or associated structures may be involved in these responses. Rats were prefed a low-protein diet. On the first experimental day, tropisetron or saline was given intraperitoneally 1 h before presentation of Imb. Cuts including the ventral branch, i.e., TVAGX, ventral vagotomy (above the hepatic branch), and hepatic + gastric vagotomies (but not hepatic branch cuts alone) caused the highest (P < 0.05) Imb intake on day 1 with or without tropisetron. The responses to tropisetron were not affected significantly. On days 2-8, groups having vagotomies that included the hepatic branch recovered faster than sham-treated animals. Because the hepatic and gastric branches together account for most of the vagal innervation to the proximal duodenum, this area may be important in the initial responses, whereas structures served by the hepatic branch alone apparently act in the later adaptation to Imb.

Effects of dorsomedial hypothalamic nuclei lesions on intake of an imbalanced amino acid diet.

Within 3 h of ingesting an imbalanced amino acid diet (Imb), rats show attenuated intake, which can be ameliorated by prior administration of the serotonin receptor antagonist tropisetron (Trop). Earlier work in which the dorsomedial hypothalamic nucleus (DMN) was electrolytically lesioned (DMNL) determined that this structure plays a role in the early detection of and subsequent adaptation to Imb. However, that study did not address whether cell bodies in the DMN, fibers of passage, or both were involved in the DMNL response to Imb. In the present investigation in experiment 1, rats were given electrolytic DMNL or a sham operation (Sham). The rats were injected with saline (Sal) or Trop just before introduction of Imb. By 3 h Sal-DMNL rats consumed more Imb than did the Sal-Sham rats; intake was normal by 12 h. Trop enhanced Imb intake, with Trop and DMNL being additive. By day 4 the DMNL rats were eating and gaining weight less than were Sham rats. In experiment 2, DMN cell bodies were destroyed by ibotenic acid (Ibo). Sal-injected Ibo-lesioned and Sham rats showed similar food intake depression on Imb; Trop similarly increased Imb intake in both groups. By day 4 both Ibo-L rats were eating and gaining weight less than were Sham rats. In experiment 3, groups of rats were given knife cuts posterior, lateral, ventral, dorsal, or anterior to the DMN. During the first 3 h of consuming Imb, all cuts except posterior enhanced the intake of Imb. Over the next 24 h the anterior cut group continued to eat more Imb than did the Sham rats. In experiment 4 DMNL rats were given novel diets; the DMNL rats did not display a neophilic response. The data suggest that fiber tracts that pass through the DMN may be involved in the early detection of Imb. DMN cell bodies, or fibers of passage, are not involved in the Trop effect. Finally, DMN cell bodies are necessary for proper long-term adaptation to Imb.