RESUMEN

BACKGROUND: Chronic pain conditions are highly prevalent in patients with mild traumatic brain injury. Supraspinal diffuse axonal injury is known to dissociate brain functional connectivity in these patients. The effect of this dissociated state on supraspinal pain network is largely unknown. A functional magnetic resonance imaging study was conducted to compare the supraspinal pain network in patients with mild traumatic brain injury to the gender and age-matched healthy controls with the hypothesis that the functional connectivities of the medial prefrontal cortices, a supraspinal pain modulatory region to other pain-related sensory discriminatory and affective regions in the mild traumatic brain injury subjects are significantly reduced in comparison to healthy controls. RESULTS: The mild traumatic brain injury group (N = 15) demonstrated significantly (P < 0.01, cluster threshold > 150 voxels) less activities in the thalamus, pons, anterior cingulate cortex, insula, dorsolateral prefrontal cortex, and medial prefrontal cortices than the healthy control group (N = 15). Granger Causality Analyses (GCA) indicated while the left medial prefrontal cortices of the healthy control group cast a noticeable degree of outward (to affect) causality inference to multiple pain processing related regions, this outward inference pattern was not observed in the mild traumatic brain injury group. On the other hand, only patients' bilateral anterior cingulate cortex received multiple inward (to be affected) causality inferences from regions including the primary and secondary somatosensory cortices and the inferior parietal lobe. Resting state functional connectivity analyses indicated that the medial prefrontal cortices of the mild traumatic brain injury group demonstrated a significantly (P < 0.01, F = 3.6, cluster size > 150 voxels) higher degree of functional connectivity to the inferior parietal lobe, premotor and secondary somatosensory cortex than the controls. Conversely, the anterior cingulate cortex of the healthy group demonstrated significantly (P < 0.01, F = 3.84, cluster size > 150 voxels) less degree of functional connectivities to the inferior parietal lobe and secondary somatosensory cortex than their mild traumatic brain injury counterparts. CONCLUSIONS: In short, the current study demonstrates that patients with mild traumatic brain injury and headaches appear to have an altered state of supraspinal modulatory and affective functions related to pain perception.

Asunto(s)

Lesiones Traumáticas del Encéfalo/fisiopatología , Encéfalo/fisiopatología , Vías Nerviosas/fisiopatología , Percepción del Dolor/fisiología , Dolor/fisiopatología , Adulto , Lesiones Traumáticas del Encéfalo/complicaciones , Mapeo Encefálico/métodos , Enfermedad Crónica , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador/métodos , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Dolor/etiología

RESUMEN

Nociceptive information is modulated by a large number of endogenous signaling agents that change over the course of recovery from injury. This plasticity makes understanding regulatory mechanisms involved in descending inhibition of pain scientifically and clinically important. Neurons that synthesize the neuropeptide TIP39 project to many areas that modulate nociceptive information. These areas are enriched in its receptor, the parathyroid hormone 2 receptor (PTH2R). We previously found that TIP39 affects several acute nociceptive responses, leading us to now investigate its potential role in chronic pain. Following nerve injury, both PTH2R and TIP39 knockout mice developed less tactile and thermal hypersensitivity than controls and returned to baseline sensory thresholds faster. Effects of hindpaw inflammatory injury were similarly decreased in knockout mice. Blockade of α-2 adrenergic receptors increased the tactile and thermal sensitivity of apparently recovered knockout mice, returning it to levels of neuropathic controls. Mice with locus coeruleus (LC) area injection of lentivirus encoding a secreted PTH2R antagonist had a rapid, α-2 reversible, apparent recovery from neuropathic injury similar to the knockout mice. Ablation of LC area glutamatergic neurons led to local PTH2R-ir loss, and barley lectin was transferred from local glutamatergic neurons to GABA interneurons that surround the LC. These results suggest that TIP39 signaling modulates sensory thresholds via effects on glutamatergic transmission to brainstem GABAergic interneurons that innervate noradrenergic neurons. TIP39's normal role may be to inhibit release of hypoalgesic amounts of norepinephrine during chronic pain. The neuropeptide may help maintain central sensitization, which could serve to enhance guarding behavior.

Asunto(s)

Inflamación/fisiopatología , Neuralgia/fisiopatología , Neuropéptidos/fisiología , Receptor de Hormona Paratiroídea Tipo 2/fisiología , Animales , Femenino , Neuronas GABAérgicas/metabolismo , Transportador de Glucosa de Tipo 2/genética , Transportador de Glucosa de Tipo 2/metabolismo , Ácido Glutámico/metabolismo , Miembro Posterior/patología , Miembro Posterior/fisiopatología , Hiperalgesia/genética , Hiperalgesia/fisiopatología , Inflamación/genética , Locus Coeruleus/citología , Locus Coeruleus/metabolismo , Masculino , Ratones , Ratones Noqueados , Ratones Transgénicos , Neuralgia/genética , Neuronas/metabolismo , Neuropéptidos/genética , Neuropéptidos/metabolismo , Dimensión del Dolor , Receptor de Hormona Paratiroídea Tipo 2/genética , Receptor de Hormona Paratiroídea Tipo 2/metabolismo , Receptores Adrenérgicos alfa 2/genética , Receptores Adrenérgicos alfa 2/metabolismo , Transducción de Señal/genética , Transducción de Señal/fisiología

RESUMEN

While the pedagogical benefits of incorporating inquiry driven labs into an undergraduate curriculum are well established, often the prohibitive costs of providing equipment for such labs limits the types of experiences that can be offered. For example, the lab portion of Advanced Neuroscience at Centenary College of Louisiana consists of a semester-long research project developed by the students. Frequently, these junior- and senior-level students generate interesting research questions that must be culled or scaled back simply due to a lack of appropriate equipment. In the most recent iteration of the class, the students wanted to examine analgesia using the tail flick test, a measure of spinal nociception. In this test a rodent subject is restrained; its tail is exposed to a heat source; and the latency to flick its tail away from the noxious stimuli is recorded. As commercial devices were far beyond the lab budget, we sought to develop an inexpensive tail flick analgesia meter that was easy to use and generated reliable data. The prototype device was tested by students in the above-mentioned class and was found to consistently produce reliable data in agreement with the literature. Here we present plans for a tail flick analgesia meter that can be constructed for $50-75, roughly 100 times cheaper than commercial devices.