Sonogenetic control of mammalian cells using exogenous Transient Receptor Potential A1 channels.

Ultrasound has been used to non-invasively manipulate neuronal functions in humans and other animals. However, this approach is limited as it has been challenging to target specific cells within the brain or body. Here, we identify human Transient Receptor Potential A1 (hsTRPA1) as a candidate that confers ultrasound sensitivity to mammalian cells.

Neuropathic Pain After Spinal Cord Injury: Challenges and Research Perspectives.

Neuropathic pain is a debilitating consequence of spinal cord injury (SCI) that remains difficult to treat because underlying mechanisms are not yet fully understood. In part, this is due to limitations of evaluating neuropathic pain in animal models in general, and SCI rodents in particular. Though pain in patients is primarily spontaneous, with relatively few patients experiencing evoked pains, animal models of SCI pain have primarily relied upon evoked withdrawals.

Analysis of the behavioral, cellular and molecular characteristics of pain in severe rodent spinal cord injury.

Human SCI is frequently associated with chronic pain that is severe and refractory to medical therapy. Most rodent models used to assess pain outcomes in SCI apply moderate injuries to lower thoracic spinal levels, whereas the majority of human lesions are severe in degree and occur at cervical or upper thoracic levels. To better model and understand mechanisms associated with chronic pain after SCI, we subjected adult rats to T3 severe compression or complete transection lesions, and examined pain-related behaviors for three months.

Induced pluripotent stem cell-derived neural stem cell therapies for spinal cord injury.

The greatest challenge to successful treatment of spinal cord injury is the limited regenerative capacity of the central nervous system and its inability to replace lost neurons and severed axons following injury. Neural stem cell grafts derived from fetal central nervous system tissue or embryonic stem cells have shown therapeutic promise by differentiation into neurons and glia that have the potential to form functional neuronal relays across injured spinal cord segments. However, implementation of fetal-derived or embryonic stem cell-derived neural stem cell therapies for patients with spinal cord injury raises ethical concerns.

Remodelling of spared proprioceptive circuit involving a small number of neurons supports functional recovery.

Studies show that limited functional recovery can be achieved by plasticity and adaptation of the remaining circuitry in partial injuries in the central nervous system, although the new circuits that arise in these contexts have not been clearly identified or characterized. We show here that synaptic contacts from dorsal root ganglions to a small number of dorsal column neurons, a caudal extension of nucleus gracilis, whose connections to the thalamus are spared in a precise cervical level 1 lesion, underwent remodeling over time. These connections support proprioceptive functional recovery in a conditioning lesion paradigm, as silencing or eliminating the remodelled circuit completely abolishes the recovered proprioceptive function of the hindlimb.

Painful neuropathy: Mechanisms.

Painful neuropathy, like the other complications of diabetes, is a growing healthcare concern. Unfortunately, current treatments are of variable efficacy and do not target underlying pathogenic mechanisms, in part because these mechanisms are not well defined. Rat and mouse models of type 1 diabetes are frequently used to study diabetic neuropathy, with rats in particular being consistently reported to show allodynia and hyperalgesia.

Animal models of diabetes-induced neuropathic pain.

Neuropathy will afflict over half of the approximately 350 million people worldwide who currently suffer from diabetes and around one-third of diabetic patients with neuropathy will suffer from painful symptoms that may be spontaneous or stimulus evoked. Diabetes can be induced in rats or mice by genetic, dietary, or chemical means, and there are a variety of well-characterized models of diabetic neuropathy that replicate either type 1 or type 2 diabetes. Diabetic rodents display aspects of sensorimotor dysfunction such as stimulus-evoked allodynia and hyperalgesia that are widely used to model painful neuropathy.