Differential Activation of Colonic Afferents and Dorsal Horn Neurons Underlie Stress-Induced and Comorbid Visceral Hypersensitivity in Female Rats.

Chronic Overlapping Pain Conditions, including irritable bowel syndrome (IBS) and temporomandibular disorder (TMD), represent a group of idiopathic pain conditions that likely have peripheral and central mechanisms contributing to their pathology, but are poorly understood. These conditions are exacerbated by stress and have a female predominance. The presence of one condition predicts the presence or development of additional conditions, making this a significant pain management problem.

Peripheral mechanisms contribute to comorbid visceral hypersensitivity induced by preexisting orofacial pain and stress in female rats.

Background: Stress exacerbates many chronic pain syndromes including irritable bowel syndrome (IBS). Among these patient populations, many suffer from comorbid or chronic overlapping pain conditions and are predominantly female. Nevertheless, basic studies investigating chronic psychological stress-induced changes in pain sensitivity have been mostly carried out in male rodents.

A clinically relevant animal model of temporomandibular disorder and irritable bowel syndrome comorbidity.

Unlabelled: Temporomandibular disorder and irritable bowel syndrome are comorbid functional chronic pain disorders of unknown etiology that are triggered/exacerbated by stress. Here we present baseline phenotypic characterization of a novel animal model to gain insight into the underlying mechanisms that contribute to such comorbid pain conditions. In this model, chronic visceral hypersensitivity, a defining symptom of irritable bowel syndrome, is dependent on 3 factors: estradiol, existing chronic somatic pain, and stress.

Repeated muscle injury as a presumptive trigger for chronic masticatory muscle pain.

skeletal muscles sustain a significant loss of maximal contractile force after injury, but terminally damaged fibers can eventually be replaced by the growth of new muscle (regeneration), with full restoration of contractile force over time. After a second injury, limb muscles exhibit a smaller reduction in maximal force and reduced inflammation compared with that after the initial injury (i.e.

Physiological, morphological and neurochemical characterization of neurons modulated by movement.

The role of individual neurons and their function in neuronal circuits is fundamental to understanding the neuronal mechanisms of sensory and motor functions. Most investigations of sensorimotor mechanisms rely on either examination of neurons while an animal is static or record extracellular neuronal activity during a movement. While these studies have provided the fundamental background for sensorimotor function, they either do not evaluate functional information which occurs during a movement or are limited in their ability to fully characterize the anatomy, physiology and neurochemical phenotype of the neuron.

Eccentric muscle contraction and stretching evoke mechanical hyperalgesia and modulate CGRP and P2X(3) expression in a functionally relevant manner.

Non-invasive, movement-based models were used to investigate muscle pain. In rats, the masseter muscle was rapidly stretched or electrically stimulated during forced lengthening to produce eccentric muscle contractions (EC). Both EC and stretching disrupted scattered myofibers and produced intramuscular plasma extravasation.

Downregulation of selective microRNAs in trigeminal ganglion neurons following inflammatory muscle pain.

Active regulation of gene expression in the nervous system plays an important role in the development and/or maintenance of inflammatory pain. MicroRNA (miRNA) negatively regulates gene expression via posttranscriptional or transcriptional inhibition of specific genes. To explore the possible involvement of miRNA in gene regulation during inflammatory pain, we injected complete Freund's adjuvant (CFA) unilaterally into the rat masseter muscle and quantified changes in neuron-specific mature miRNAs in the trigeminal ganglion (TG).

Nociceptive craniofacial muscle primary afferent neurons synapse in both the rostral and caudal brain stem.

Limited information is available on muscle afferent neurons with fine fibers despite their presumed participation in musculoskeletal disorders, including temporomandibular disorders. To study these neurons, intracellular recordings were made from the central axons of slowly conducting muscle afferent neurons in anesthetized rats. After intraaxonal impalement, axons were characterized by masseter nerve stimulation, receptive field testing, muscle stretching and intramuscular injection of hypertonic saline.

Classification of muscle spindle afferents innervating the masseter muscle in rats.

Taylor et al. [Taylor, A., Durbaba, R.

Inflammation of craniofacial muscle induces widespread mechanical allodynia.

The modulation of behavioral responses evoked by local and distant nociceptive stimuli following a discrete somatic injection of complete Freund's adjuvant (CFA) was examined in rats. Inflammation of one craniofacial muscle evoked mechanical allodynia not only in the region of inflammation but also secondary mechanical allodynia in the contralateral head, ipsilateral hindpaw, and contralateral hindpaw. In contrast to this, CFA-induced inflammation of either the hindpaw or gastrocnemius muscle evoked mechanical allodynia restricted to the hindlimb region.

Deep tissue inflammation upregulates neuropeptides and evokes nociceptive behaviors which are modulated by a neuropeptide antagonist.

Promising recent developments in the therapeutic value of neuropeptide antagonists have generated renewed importance in understanding the functional role of neuropeptides in nociception and inflammation. To explore this relationship we examined behavioral changes and primary afferent neuronal plasticity following deep tissue inflammation. One hour following craniofacial muscle inflammation ipsilateral as well as contralateral head withdrawal thresholds and ipsi- and contralateral hindpaw withdrawal thresholds were lowered and remained reduced for 28 days.

Trigeminal P2X3 receptor expression differs from dorsal root ganglion and is modulated by deep tissue inflammation.

The distribution and modulation of the P2X(3) receptor was studied in trigeminal ganglion neurons to provide insight into the role of ATP in craniofacial sensory mechanisms. Binding to the d-galactose specific lectin IB4 was found in 73% of P2X(3)-positive neurons while only 16% of IB4 neurons expressed P2X(3). Neurons expressing P2X(3) alone were significantly larger than IB4-or IB4/P2X(3)-positive neurons.

Chemical phenotypes of muscle and cutaneous afferent neurons in the rat trigeminal ganglion.

Retrograde labeling was combined with cytochemistry to investigate phenotypic differences in primary afferent neurons relaying sensory information from deep and superficial craniofacial tissues. Calcitonin gene-related peptide (CGRP), substance P (SP), somatostatin (SOM) immunoreactivity and isolectin IB4, and cholera toxin B (ChTB) binding were examined for trigeminal masticatory muscle and cutaneous afferent neurons. Somata labeled from muscle were larger than cutaneous afferent neurons.