Effects of diet-induced obesity on motivation and pain behavior in an operant assay.

Obesity has been associated with multiple chronic pain disorders, including migraine. We hypothesized that diet-induced obesity would be associated with a reduced threshold for thermal nociception in the trigeminal system. In this study, we sought to examine the effect of diet-induced obesity on facial pain behavior. Mice of two different strains were fed high-fat or regular diet (RD) and tested using a well-established operant facial pain assay. We found that the effects of diet on behavior in this assay were strain and reward dependent. Obesity-prone C57BL/6J mice fed a high-fat diet (HFD) display lower number of licks of a caloric, palatable reward (33% sweetened condensed milk or 30% sucrose) than control mice. This occurred at all temperatures, in both sexes, and was evident even before the onset of obesity. This diminished reward-seeking behavior was not observed in obesity-resistant SKH1-E (SK) mice. These findings suggest that diet and strain interact to modulate reward-seeking behavior. Furthermore, we observed a difference between diet groups in operant behavior with caloric, palatable rewards, but not with a non-caloric neutral reward (water). Importantly, we found no effect of diet-induced obesity on acute thermal nociception in the absence of inflammation or injury. This indicates that thermal sensation in the face is not affected by obesity-associated peripheral neuropathy as it occurs when studying pain behaviors in the rodent hindpaw. Future studies using this model may reveal whether obesity facilitates the development of chronic pain after injury or inflammation.

Obesity increases nociceptive activation of the trigeminal system.

BACKGROUND: Obesity is a risk factor associated with several pain syndromes. However, the mechanisms underlying the association between obesity and pain are not known. The aim of this study was to test the hypothesis that obesity enhances neuronal responses to nociceptive stimulation within the trigeminal nucleus caudalis (TNC). METHODS: Male and female C57BL/6J mice were fed a high-fat or regular diet from the time of weaning until 20 weeks of age. We then quantified neuronal activation by measuring Fos immunoreactivity within the TNC in response to a facial injection of a low dose of capsaicin (1 µg/10 µL). RESULTS: We found that 0.01% capsaicin did not significantly increase Fos immunoreactivity in control mice fed a regular diet. In contrast, this low dose of capsaicin caused a 3.3-fold increase in Fos in the TNC in obese mice (p < 0.001). CONCLUSIONS: These results support the hypothesis that diet-induced obesity in mice enhances nociceptive processing within the TNC. Diet-induced obesity may be a useful model for mechanistic studies. Future studies will improve our understanding of how obesity may contribute to trigeminal pain by sensitizing the trigeminal nociceptive system.

Characterization of bilateral trigeminal constriction injury using an operant facial pain assay.

In order to better understand and treat neuropathic pain, scientific study must use methods that can assess pain processing at the cortical level where pain is truly perceived. Operant behavior paradigms can accomplish this. We used an operant task to evaluate changes following chronic constriction injury to the trigeminal nerves. We also relate these behavioral changes to immunohistochemistry of transient receptor potential channels vanilloid 1 and melastatin 8 (TRPV1 and TRPM8) in the trigeminal ganglia. Following nerve injury, successful performance of the operant task was reduced and aversive behaviors were observed with 10 and 37 °C stimulation, indicating cold allodynia and mechanical allodynia respectively. In contrast, while aversive behaviors were observed with 48 °C stimulation, successful performance of the operant task was not substantially hindered following injury. These behavioral changes were accompanied by an increase in TRPV1 positive cells and an increased intensity of TRPM8 staining at 2 weeks post-injury, when cold allodynia is maximal. These findings suggest that the incorporation of operant behavioral assessment in the study of pain may provide insight into the relationship among peripheral changes, motivational drive, and pain. Understanding this relationship will allow us to better treat and prevent chronic neuropathic pain.

Intraoperative sestamibi scanning in reoperative parathyroidectomy.

BACKGROUND: Reoperative neck exploration for hyperparathyroidism is often difficult even for experienced surgeons. Recent advances in preoperative and intraoperative localization techniques have improved successful resection rates. This prospective study evaluates the accuracy and clinical utility of intraoperative technetium 99m sestamibi scanning for localizing hyperfunctioning parathyroid tissue in reoperative neck explorations. PATIENTS AND METHODS: Eleven patients underwent reoperative neck exploration for hyperparathyroidism. Two patients had 3 prior neck explorations, 1 had 2 prior neck explorations, and 8 patients had 1 prior neck operation. Preoperative studies included sestamibi scintigraphy and ultrasound in all patients, magnetic resonance imaging in 4, computed tomography scan in 3, parathyroid arteriogram in 1, and selective venous sampling in 1. All patients underwent intraoperative technetium 99m sestamibi scanning and parathyroid hormone assay. RESULTS: Preoperative technetium 99m sestamibi scanning and ultrasound each successfully localized 7 of 11 hyperfunctioning glands (64%). Intraoperative technetium 99m sestamibi scanning correctly localized 10 of 11 hyperfunctioning glands (91%). Intraoperative parathyroid hormone assay confirmed successful excision of hyperfunctioning tissue in all 11 patients. Postoperatively, all 11 patients had low-normal or normal calcium levels. CONCLUSIONS: Intraoperative technetium 99m sestamibi correctly localized 91% of hyperfunctioning glands compared with 64% localization for preoperative technetium 99m sestamibi and preoperative ultrasound. Intraoperative technetium 99m sestamibi scanning and parathyroid hormone monitoring are useful in reoperative neck explorations for hyperparathyroidism.

New technique for reapproximation of the calcaneofibular ligament after double ligament rupture.

Ankle sprains are often inadequately treated in the emergency room, because of the feeling that, "It is only a sprain." A thorough examination is performed at St. John Hospital Macomb Center to determine the extent of ligamentous damage. If a double ligament rupture presents, and surgical intervention is necessary, a procedure similar to the one described by Bröstrom is performed. The calcaneofibular ligament's frayed ends, as well as its location, make suturing the ligament difficult. Utilizing medium-sized Ligaclips on either side of the rupture provides an excellent scaffold for reapproximation of the calcaneofibular ligament. The Ligaclips could also be used to determine if a re-rupture has occurred.