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.

HPLC-purified bovine satietin suppresses food intake and weight without causing conditioned taste aversion.

Satietin (SAT) is a putative satiety agent found in a variety of species including man and the rat. In the present study, satietin was extracted from bovine plasma (b-SAT) and further high-pressure liquid chromatography (HPLC)-purified. Rats were given chronic third ventricle cannulas and patency was verified. In experiment 1, rats were divided into three groups and ICV infused with artificial cerebrospinal fluid (a-CSF) or b-SAT: group 1, a-CSF (n = 11); group 2, 20 micrograms/rat, b-SAT (n = 11); and group 3, 40 micrograms/rat, b-SAT (n = 9). Infusions were repeated thrice three days apart. Compared to a-CSF, the high b-SAT dose suppressed food intake for 24-h after each successive infusion. The low dose significantly decreased food intake only after the first infusion. Water intake was suppressed only after the first injection of the high dose. Body weight was decreased after the first and second infusions of both doses and following the third infusion of the high dose. In experiment 2, rats were trained to drink fluid for 1 h/day while food was ad lib. On day 1, both groups received no infusions and were given tap water. On day 2, the groups were ICV infused with a-CSF, but group 1 (n = 12) was given banana-flavored fluid (BFF) and group 2 (n = 12) almond-flavored fluid (AFF). On day 3, group 1 was again a-CSF-infused but given AFF, whereas group 2 received 40 micrograms/rat b-SAT and was given BFF.(ABSTRACT TRUNCATED AT 250 WORDS)

Suppression of feeding by cholecystokinin but not bombesin is attenuated in dorsomedial hypothalamic nuclei lesioned rats.

Rats with dorsomedial hypothalamic lesions (DMN-L) or sham operations were injected IP with saline or the satiety peptide cholecystokinin (CCK) at 3.0 and 6.0 micrograms/kg at the onset of the dark phase. Food consumption was then measured 15, 30 and 60 min later. Compared to saline baseline intake, CCK suppressed feeding during the first 30 min following injection in the sham operated group but not in the DMN-L group. Bombesin (BBS), another satiety peptide was also injected (4.0 and 8.0 micrograms/kg) into the two groups. BBS produced significant and comparable suppression of feeding in both DMN-L and sham operated rats. In a third trial a large dose of CCK (12.0 micrograms/kg) was injected into the two groups as described above. The CCK suppressed feeding for 60 min in the control group. CCK also attenuated feeding in the DMN-L group, but for only 30 min. However, even this suppression was reduced compared to the control group. The data suggest that the DMN may play a role in CCK induced satiety.

Nutritional studies in the weanling rat with normophagic hypothalamic obesity.

Weanling male hypothalamic-obese Sprague-Dawley rats (VMNL) and sham-operated controls (CON) fed stock diet for 2 weeks postoperatively ate similar amounts, but VMNL laid down more fat and less body weight per calories. Three equicaloric diets of different macronutrient (MN) content each were fed for 21 days. Diet selection: VMNL selected more carbohydrate (CHO) diet and protein diet but similar amounts of fat diet; total caloric intake was comparable. Percent diet selection showed the identical pattern. MN intake: VMNL ingested more percent CHO, less percent protein and similar percent fat as CON. Refeeding after 2-day fast: both groups selected similar amounts of diets, but VMNL ingested less protein. High protein diet along (9 days): both groups increased caloric intake over previous regimens, weight gain and caloric intake were similar, but Lee Index was higher in VMNL. Stock diet (32 days): VMNL showed normal body weight gains but higher Lee Index despite hypophagia. They utilized calories similarly for body weight gains but more poorly for fat deposition than CON. After death several key plasma substrates were similar in both groups but epididymal fat pads were heavier in VMNL.

Water regulation in weanling hypodipsic dorsomedial hypothalamic-lesioned rats.

Weanling rats with dorsomedial hypothalamic nuclei lesions (DMN-L) are hypodipsic and hypophagic when compared to sham-operated rats. When tested for interdependence of food and water intake (WI) the DMN-L rats drank in the absence of food and ate in the absence of water. The data suggest DMN-L rats are not prandial drinkers. On testing for intracellular thirst (5.8 or 5.4% NaCl, 1 ml/100 g body wt), extracellular thirst [polyethylene glycol (PG), 25% wt/vol, 0.5 ml/35 g body wt], or a combination of both thirsts, the DMN-L rats responded as well or better than the control animals when the test data were expressed as a percentage of the rat's base-line WI. Both groups were more responsive to PG when tested in the light phase. When injected with angiotensin II (200 micrograms/100 g body wt) both groups responded similarly. Therefore, whereas the DMN-L rats were hypodipsic in comparison to controls, they respond as well or better than control animals when classical thirst testing procedures are utilized. It is suggested that DMN-L may have "reset" WI similarly to the previously proposed reset for body weight and food intake.

Response of growth-retarded, hypophagic-hypodipsic rats with dorsomedial hypothalamic lesions to a diet in liquid and powder forms.

Weanling rats with dorsomedial hypothalamic lesions (DMNL rats) and sham-operated controls exhibited significantly reduced food intake and ponderal and linear growth during an 11-day post-operative period on lab chow. For 28 days, a synthetic liquid diet (Liquid) was fed to one DMNL and one control group; a second DMNL and control group received the same diet in a powder form (Powder). DMNL rats remained hypophagic on either diet but DMNL and control rats fed Liquid ate significantly more than their counterparts fed Powder. Total fluid intake pattern was identical to caloric intake. For 27 days all groups again received lab chow. They reverted to the caloric intake pattern shown during the 11-day post-operative period. Body weight gains paralleled the caloric and fluid intake patterns except that during the synthetic diet period the Liquid-fed controls outgained all other groups and that there was no difference between DMNL rats on Liquid and Powder. At sacrifice, plasma glucose, glycerol, free fatty acids and total protein were similar in all groups but carcass protein was higher in the DMNL rats formerly fed Liquid. DMNL rats behave in accordance with extensive previous data that led to the formulation of a "resetting" hypothesis.

Further nutritional characterization of dorsomedial hypothalamic hypophagia in rats: diet consistency, finickiness, self-selection of diets, starvation and realimentation and "stress eating".

Young-mature male Sprague-Dawley rats received bilateral lesions in the dorsomedial hypothalamic nuclei (DMNL); sham-operated rats served as controls. After 30 days of a pelleted commercial laboratory diet, they received a powdered lab diet for 10 days. Both groups of rats reduced food intake for the duration of the test. Thus, although grossly hypophagic under ad libitum feeding conditions, DMNL do not impair adaptation to a diet of different consistency. Both DMNL and controls were significantly hypophagic when fed a quinine-adulterated powdered diet, but only on the first of a 9-day regimen. Thus, they show only transitory finickiness. During a 16-day self-selection test with three equicaloric diets with different amounts of the three macronutrients in each (HCD: high carbohydrate, HFD: high fat, and HPD: high protein diet), DMNL rats ate in absolute terms (g/day) the same amount of HCD, significantly less HFD and during two of seven measuring periods, significantly less HPD. However, their intake in percent of total consumption was similar to that of the controls., After a 48-hour fast, DMNL rats lost and regained body though these rats showed hypophagia during the 48-hour realimentation period, their efficiency of food utilization was similar to the controls. Thus, DMNL rats have not lost the capacity to regulate body weight and food intake after fast-induced weight loss. During eight tail pinch (TP) sessions (11 days), DMNL rats were hyperphagic and preferred HCD and HFD in comparison with controls. In their home cages (lab diet) DMNL rats were hypophagic and over 11 days showed a decline in food intake while the controls displayed an increase. In contrast to previous findings, the challenges of the present study unmasked some deficits in energy homeostasis in the DMNL rat.

Relative normophagia and organ growth in growth-retarded weanling rats with dorsomedial hypothalamic lesions.

Weanling rats with ventromedial (VMNL) and dorsomedial (DMNL) hypothalamic lesions and sham-operated controls were maintained up to 198 days after operation. Food intake was measured throughout the experiment and organ weights were recorded at various periods of sacrifice. Comparisons were made between controls and VMNL and DMNL rats, respectively. Food intake and organ weights were expressed in absolute terms and relative to body mass and Kleiber's "metabolic size." VMNL rats were always normophagic and showed lower organ weights, regardless of manner of computation. Rats with DMNL, on the other hand, were absolutely hypophagic but relatively normophagic for considerable periods of time when food intake was referred to body mass. A similar relationship obtained for organ weights. The data fit well with previous results and with a hypothesis that holds that DMNL bring about a "resetting" of some central nervous control system that not only allows the rat so operated to subsist on lower substrate levels but also regulates normal growth in relation to body mass.

Feeding responses of rats with dorsomedial hypothalamic lesions given ip 2DG or glucose.

The glucoprivation effects of 2-deoxy-D-glucose (2DG) on feeding behavior were studied in rats with bilateral lesions of the dorsomedial hypothalamic nucleus (DMN) and sham-operated controls. The lesioned and sham-operated rats were injected intraperitoneally with 2DG (5% wt/vol) at doses of either 150 mg/kg, 300 mg/kg, or 500 mg/kg, or with saline ("control days"). At all doses significantly more sham-operated rats ate and showed an increased food consumption during the first few hours after 2DG injection when compared to saline control days. However, their 24-h food consumption was normal or less than normal, depending on the dose of 2DG. On the other hand, rats with DMN lesions (DMN-L) did not increase their food consumption during the 4 h after the injection at any of the 2DG doses. In a second experiment DMN-L and sham-operated controls were injected intraperitoneally with glucose (1.36 g/kg body wt or 2.72 g/kg body wt) or saline after an overnight fast. Glucose loads, compared to saline injections, significantly depressed the controls' food consumption only during the first hour of refeeding. On the other hand, glucose injections did not depress food intake of the DMN-L rats. It is suggested that DMN lesions may have either destroyed glucoreceptors in the DMN that monitor glucose or the glucoprivation effects caused by 2DG and/or glucoreceptive pathways that pass through the DMN.