Thermally induced neuronal plasticity in the hypothalamus mediates heat tolerance.

Heat acclimation is an adaptive process that improves physiological performance and supports survival in the face of increasing environmental temperatures, but the underlying mechanisms are not well understood. Here we identified a discrete group of neurons in the mouse hypothalamic preoptic area (POA) that rheostatically increase their activity over the course of heat acclimation, a property required for mice to become heat tolerant. In non-acclimated mice, peripheral thermoafferent pathways via the parabrachial nucleus activate POA neurons and mediate acute heat-defense mechanisms.

Stomatin-like protein 3 modulates the responses of Aδ, but not C fiber bone afferent neurons to noxious mechanical stimulation in an animal model of acute experimental bone pain.

STOML3 is a membrane bound scaffolding protein that has been shown to facilitate the opening of mechanically sensitive ion channels and contribute to noxious mechanical sensation, allodynia and hyperalgesia. In this study, we aimed to determine the role of STOML3 in noxious mechanical sensitivity of bone afferent neurons and carrageenan-induced acute inflammation in the bone. An electrophysiological bone-nerve preparation was used to make recordings of the activity and sensitivity of bone afferent neurons that innervate the tibial marrow cavity in anaesthetised rats, in response to noxious mechanical stimuli delivered to the marrow cavity, before and after injection of either the STOML3 oligomerisation inhibitor OB-1 or vehicle, in either naïve animals or animals with carrageenan-induced inflammation of the marrow cavity.

A synaptic temperature sensor for body cooling.

Deep brain temperature detection by hypothalamic warm-sensitive neurons (WSNs) has been proposed to provide feedback information relevant for thermoregulation. WSNs increase their action potential firing rates upon warming, a property that has been presumed to rely on the composition of thermosensitive ion channels within WSNs. Here, we describe a synaptic mechanism that regulates temperature sensitivity of preoptic WSNs and body temperature.

Piezo2 Knockdown Inhibits Noxious Mechanical Stimulation and NGF-Induced Sensitization in A-Delta Bone Afferent Neurons.

Piezo2 is a mechanically gated ion-channel that has a well-defined role in innocuous mechanical sensitivity, but recently has also been suggested to play a role in mechanically induced pain. Here we have explored a role for Piezo2 in mechanically evoked bone nociception in Sprague Dawley rats. We have used an electrophysiological bone-nerve preparation to record the activity of single Aδ bone afferent neurons in response to noxious mechanical stimulation, after Piezo2 knockdown in the dorsal root ganglia with intrathecal injections of Piezo2 antisense oligodeoxynucleotides, or in control animals that received mismatch oligodeoxynucleotides.

TRPV1 activation alters the function of Aδ and C fiber sensory neurons that innervate bone.

The Transient receptor potential cation channel subfamily V member 1 (TRPV1) is a non-selective cation channel that is activated by capsaicin, low pH and noxious heat. It has been suggested to have a pro-algesic role in a range of conditions that present with bone pain, but the mechanisms by which this occurs are not yet clear. In this study we aimed to determine if TRPV1 is expressed in Aδ and/or C fiber bone afferent neurons, and to explore its role in the activation and/or sensitization of bone afferent neurons to mechanical stimulation.

Sequestration of artemin reduces inflammation-induced activation and sensitization of bone marrow nociceptors in a rodent model of carrageenan-induced inflammatory bone pain.

Background: Pathologies that affect the bone marrow have a significant inflammatory component; however, it is not clear how inflammatory mediators affect nociceptive nerve terminals within the marrow cavity.

Methods: In this study, an in vivo bone-nerve preparation was used to directly record the physiological response properties of bone marrow nociceptors innervating the tibial marrow cavity of rats, before and after application of the inflammatory agent carrageenan. In addition, endogenous artemin was sequestered by application of an artemin neutralizing antibody to determine if this could prevent the inflammation-induced physiological changes observed.

GDNF, Neurturin, and Artemin Activate and Sensitize Bone Afferent Neurons and Contribute to Inflammatory Bone Pain.

Pain associated with skeletal pathology or disease is a significant clinical problem, but the mechanisms that generate and/or maintain it remain poorly understood. In this study, we explored roles for GDNF, neurturin, and artemin signaling in bone pain using male Sprague Dawley rats. We have shown that inflammatory bone pain involves activation and sensitization of peptidergic, NGF-sensitive neurons via artemin/GDNF family receptor α-3 (GFRα3) signaling pathways, and that sequestering artemin might be useful to prevent inflammatory bone pain derived from activation of NGF-sensitive bone afferent neurons.

Mechanisms of nerve growth factor signaling in bone nociceptors and in an animal model of inflammatory bone pain.

Sequestration of nerve growth factor has been used successfully in the management of pain in animal models of bone disease and in human osteoarthritis. However, the mechanisms of nerve growth factor-induced bone pain and its role in modulating inflammatory bone pain remain to be determined. In this study, we show that nerve growth factor receptors (TrkA and p75) and some other nerve growth factor-signaling molecules (TRPV1 and Nav1.

Mechanically sensitive Aδ nociceptors that innervate bone marrow respond to changes in intra-osseous pressure.

Key Points: Sensory neurons that innervate the bone marrow provide the CNS with information about pain associated with bone disease and pathology, but little is known of their function. Here we use a novel in vivo bone-nerve electrophysiological preparation to study how they respond to noxious mechanical stimulation delivered by increasing intra-osseous pressure. We provide evidence that sensory neurons that innervate the bone marrow respond to high threshold noxious mechanical stimulation, have response properties consistent with a role in nociception, provide information about different features of an intra-osseous pressure stimulus and express the Piezo2 mechano-transducer molecule.

The Physiology of Bone Pain. How Much Do We Really Know?

Pain is associated with most bony pathologies. Clinical and experimental observations suggest that bone pain can be derived from noxious stimulation of the periosteum or bone marrow. Sensory neurons are known to innervate the periosteum and marrow cavity, and most of these have a morphology and molecular phenotype consistent with a role in nociception.

A simple stimulatory device for evoking point-like tactile stimuli: a searchlight for LFP to spike transitions.

Current neurophysiological research has the aim to develop methodologies to investigate the signal route from neuron to neuron, namely in the transitions from spikes to Local Field Potentials (LFPs) and from LFPs to spikes. LFPs have a complex dependence on spike activity and their relation is still poorly understood(1). The elucidation of these signal relations would be helpful both for clinical diagnostics (e.

Neuronal functional connection graphs among multiple areas of the rat somatosensory system during spontaneous and evoked activities.

Small-World Networks (SWNs) represent a fundamental model for the comprehension of many complex man-made and biological networks. In the central nervous system, SWN models have been shown to fit well both anatomical and functional maps at the macroscopic level. However, the functional microscopic level, where the nodes of a network are represented by single neurons, is still poorly understood.

Small-world networks in neuronal populations: a computational perspective.

The analysis of the brain in terms of integrated neural networks may offer insights on the reciprocal relation between structure and information processing. Even with inherent technical limits, many studies acknowledge neuron spatial arrangements and communication modes as key factors. In this perspective, we investigated the functional organization of neuronal networks by explicitly assuming a specific functional topology, the small-world network.