Faculty Bibliography

Tongue strength is reduced in patients treated with chemoradiotherapy for oral/oropharyngeal cancer. Tongue strengthening protocols have resulted in improved lingual strength and swallowing in healthy individuals, as well as in patients following a neurological event. However, no studies have examined the efficacy of tongue strengthening exercises on tongue strength, swallowing, and quality of life (QOL; Head and Neck Cancer Inventory) in patients treated with chemoradiotherapy. A randomized clinical trial examined the effects of a tongue strengthening programme paired with traditional exercises vs. traditional exercises alone. Dependent variables included tongue strength, swallowing, and QOL in a group of patients with oral and oropharyngeal cancer treated with primary radiotherapy with or without chemotherapy. Differences with regard to tongue strength and oropharyngeal swallow efficiency (OPSE) were not observed within or between groups. QOL in the eating and speech domains improved following treatment in both groups. However, the experimental group demonstrated greater impairment in QOL in the social disruption domain following treatment, whereas the control group demonstrated a slight improvement in functioning. Tongue strengthening did not yield a statistically significant improvement in either tongue strength or swallowing measures in this patient cohort. Patient compliance and treatment timing may be factors underlying these outcomes.

Patients, primary care doctors, neurologists and otolaryngologists often have differing views on what is truly causing headache in the sinonasal region. This review discusses common primary headache diagnoses that can masquerade as "sinus headache" or "rhinogenic headache," such as migraine, trigeminal neuralgia, tension-type headache, temporomandibular joint dysfunction, giant cell arteritis (also known as temporal arteritis) and medication overuse headache, as well as the trigeminal autonomic cephalalgias, including cluster headache, paroxysmal hemicrania, and hemicrania continua. Diagnostic criteria are discussed and evidence outlined that allows physicians to make better clinical diagnoses and point patients toward better treatment options.

BACKGROUND: Cancer pain severely limits function and significantly reduces quality of life. Subtypes of sensory neurons involved in cancer pain and proliferation are not clear. METHODS: We produced a cancer model by inoculating human oral squamous cell carcinoma (SCC) cells into the hind paw of athymic mice. We quantified mechanical and thermal nociception using the paw withdrawal assays. Neurotoxins isolectin B4-saporin (IB4-SAP), or capsaicin was injected intrathecally to selectively ablate IB4(+) neurons or TRPV1(+) neurons, respectively. JNJ-17203212, a TRPV1 antagonist, was also injected intrathecally. TRPV1 protein expression in the spinal cord was quantified with western blot. Paw volume was measured by a plethysmometer and was used as an index for tumor size. Ki-67 immunostaining in mouse paw sections was performed to evaluate cancer proliferation in situ. RESULTS: We showed that mice with SCC exhibited both mechanical and thermal hypersensitivity. Selective ablation of IB4(+) neurons by IB4-SAP decreased mechanical allodynia in mice with SCC. Selective ablation of TRPV1(+) neurons by intrathecal capsaicin injection, or TRPV1 antagonism by JNJ-17203212 in the IB4-SAP treated mice completely reversed SCC-induced thermal hyperalgesia, without affecting mechanical allodynia. Furthermore, TRPV1 protein expression was increased in the spinal cord of SCC mice compared to normal mice. Neither removal of IB4(+) or TRPV1(+) neurons affected SCC proliferation. CONCLUSIONS: We show in a mouse model that IB4(+) neurons play an important role in cancer-induced mechanical allodynia, while TRPV1 mediates cancer-induced thermal hyperalgesia. Characterization of the sensory fiber subtypes responsible for cancer pain could lead to the development of targeted therapeutics.

Abstract Background: Lymphedema (LE) is a frequent complication following breast cancer treatment. While progress is being made in the identification of phenotypic risk factors for the development of LE, little information is available on the molecular characterization of LE. The purpose of this study was to determine if variations in pro- and anti-inflammatory cytokine genes were associated with LE following breast cancer treatment. Methods and Results: Breast cancer patients completed a number of self-report questionnaires. LE was evaluated using bioimpedance spectroscopy. Genotyping was done using a custom genotyping array. No differences were found between patients with (n=155) and without LE (n=387) for the majority of the demographic and clinical characteristics. Patients with LE had a significantly higher body mass index, more advanced disease, and a higher number of lymph nodes removed. Genetic associations were identified for three genes (i.e., interleukin (IL4) 4 (rs2227284), IL 10 (rs1518111), and nuclear kappa factor beta 2 (NFKB2 (rs1056890)) associated with inflammatory responses. Conclusions: These genetic associations suggest a role for a number of pro- and anti-inflammatory genes in the development of LE following breast cancer treatment.

Animals often listen selectively for particular sounds, a strategy that could alter neural encoding mechanisms to maximize the ability to detect the target. Here, we recorded auditory cortex neuron responses in well trained, freely moving gerbils as they performed a tone detection task. Each trial was initiated by the animal, providing a predictable time window during which to listen. No sound was presented on nogo trials, permitting us to assess spontaneous activity on trials in which a signal could have been expected, but was not delivered. Immediately after animals initiated a trial, auditory cortex neurons displayed a 26% reduction in spontaneous activity. Moreover, when stimulus-driven discharge rate was referenced to this reduced baseline, a larger fraction of auditory cortex neurons displayed a detection threshold within 10 dB of the behavioral threshold. These findings suggest that auditory cortex spontaneous discharge rate can be modulated transiently during task performance, thereby increasing the signal-to-noise ratio and enhancing signal detection.