Acute effects of radiation treatment to submental muscles on burrowing and swallowing behaviors in a rat model.

Swallowing impairments are a major complication of radiation treatment for oropharyngeal cancers, influencing oral intake and quality of life. The timing and functional consequences of radiation treatment on the swallowing process is not clearly understood. A rodent radiation injury model was used to investigate the onset of oral and pharyngeal dysfunctions in deglutition related to radiation treatment. This study tested the hypothesis that (Wall et al., 2013) alterations in normal biting, licking, and swallowing performance would be measurable following 64Gy of fractionated radiation to the submental muscles; and (Kotz et al., 2004) radiation will affect the animal's general well-being as measured via burrowing activity. Seven rats received radiation using a clinical linear accelerator given in 8 fractions of 8Gy and another seven animals received sham anesthesia only treatment. Swallowing bolus transit/size was assessed via videofluoroscopy, tongue movement during drinking was measured via an electrical lick sensor, and biting was analyzed from acoustic recordings of a vermicelli pasta test. Burrowing activity was measured by the amount of gravel substrate displaced within a container. Measurements were taken at baseline, during treatment (1-4 weeks), and after completion of treatment (weeks 5 & 6). Decreases in licking frequency and increases in inter-lick interval were observed 5- and 6-weeks post-treatment. Significant decreases in burrowing performance, swallowing frequency, and inter-swallow interval were observed starting the last week of treatment and continuing up to 2-weeks after completion. Results suggest that tongue dysfunction is one of the first treatment related feeding problems to present immediately after the completion of radiation to the submental muscles.

Swallowing dysfunction following radiation to the rat mylohyoid muscle is associated with sensory neuron injury.

Radiation-based treatments for oropharyngeal and hypopharyngeal cancers result in impairments in swallowing mobility, but the mechanisms behind the dysfunction are not clear. The purpose of this study was to determine if we could establish an animal model of radiation-induced dysphagia in which mechanisms could be examined. We hypothesized that 1) radiation focused at the depth of the mylohyoid muscle would alter normal bolus transport and bolus size and 2) radiation to the mylohyoid muscle will induce an injury/stress-like response in trigeminal sensory neurons whose input might modulate swallow. Rats were exposed to 48 or 64 Gy of radiation to the mylohyoid given 8 Gy in 6 or 8 fractions. Swallowing function was evaluated by videofluoroscopy 2 and 4 wk following treatment. Neuronal injury/stress was analyzed in trigeminal ganglion by assessing activating transcription factor (ATF)3 and GAP-43 mRNAs at 2, 4, and 8 wk post treatment. Irradiated rats exhibited decreases in bolus movement through the pharynx and alterations in bolus clearance. In addition, ATF3 and GAP-43 mRNAs were upregulated in trigeminal ganglion in irradiated rats, suggesting that radiation to mylohyoid muscle induced an injury/stress response in neurons with cell bodies that are remote from the irradiated tissue. These results suggest that radiation-induced dysphagia can be assessed in the rat and radiation induces injury/stress-like responses in sensory neurons.NEW & NOTEWORTHY Radiation-based treatments for head and neck cancer can cause significant impairments in swallowing mobility. This study provides new evidence supporting the possibility of a neural contribution to the mechanisms of swallowing dysfunction in postradiation dysphagia. Our data demonstrated that radiation to the mylohyoid muscle, which induces functional deficits in swallowing, also provokes an injury/stress-like response in the ganglion, innervating the irradiated muscle.

Rapid and temporary improvement of depression and anxiety observed following niraparib administration: a case report.

BACKGROUND: Cancer patients are disproportionately affected by generalized anxiety and major depression. For many, current treatments for these conditions are ineffective. In this case report, we present a serendipitous case of anxiety and depression improvement following administration of the poly (ADP-ribose) polymerase (PARP) inhibitor niraparib. CASE PRESENTATION: A 61-year old woman with a 20-year history of mild depression developed recurrent ovarian carcinoma and was placed on niraparib for maintenance chemotherapy. With the original onset of ovarian cancer, she experienced an episode of major depression that was resolved with sertraline. After recurrence of ovarian cancer, she experienced a recurrence of major depression and a new onset of generalized anxiety that failed to completely respond to multiple medications. After beginning niraparib therapy the patient noticed a rapid resolution of the symptoms of her anxiety and depression, an effect that was limited to 10-14 days. Due to bone marrow suppression, the patient was taken off and restarted on niraparib several times. Each discontinuation of niraparib resulted in return of her depression and anxiety, while each recontinuation of niraparib resulted in an improvement in her mood and anxiety. CONCLUSIONS: This case demonstrates rapid and temporary improvement of anxiety and depression following niraparib administration. There is ample preclinical data that PARP signaling may play a role in psychiatric illness. A small amount of indirect data from clinical trials also shows that niraparib may have psychiatric benefits. Further research on PARP inhibition and its potential psychoactive effects is sorely needed.