Three functionally distinct classes of C-fibre nociceptors in primates.

In primates, C-fibre polymodal nociceptors are broadly classified into two groups based on mechanosensitivity. Here we demonstrate that mechanically sensitive polymodal nociceptors that respond either quickly (QC) or slowly (SC) to a heat stimulus differ in responses to a mild burn, heat sensitization, conductive properties and chemosensitivity. Superficially applied capsaicin and intradermal injection of β-alanine, an MrgprD agonist, excite vigorously all QCs.

Conventional and kilohertz-frequency spinal cord stimulation produces intensity- and frequency-dependent inhibition of mechanical hypersensitivity in a rat model of neuropathic pain.

Background: Spinal cord stimulation (SCS) is a useful neuromodulatory technique for treatment of certain neuropathic pain conditions. However, the optimal stimulation parameters remain unclear.

Methods: In rats after L5 spinal nerve ligation, the authors compared the inhibitory effects on mechanical hypersensitivity from bipolar SCS of different intensities (20, 40, and 80% motor threshold) and frequencies (50, 1 kHz, and 10 kHz).

Local loperamide injection reduces mechanosensitivity of rat cutaneous, nociceptive C-fibers.

Loperamide reverses signs of mechanical hypersensitivity in an animal model of neuropathic pain suggesting that peripheral opioid receptors may be suitable targets for the treatment of neuropathic pain. Since little is known about loperamide effects on the responsiveness of primary afferent nerve fibers, in vivo electrophysiological recordings from unmyelinated afferents innervating the glabrous skin of the hind paw were performed in rats with an L5 spinal nerve lesion or sham surgery. Mechanical threshold and responsiveness to suprathreshold stimulation were tested before and after loperamide (1.

A role for nociceptive, myelinated nerve fibers in itch sensation.

Despite its clinical importance, the underlying neural mechanisms of itch sensation are poorly understood. In many diseases, pruritus is not effectively treated with antihistamines, indicating the involvement of nonhistaminergic mechanisms. To investigate the role of small myelinated afferents in nonhistaminergic itch, we tested, in psychophysical studies in humans, the effect of a differential nerve block on itch produced by intradermal insertion of spicules from the pods of a cowhage plant (Mucuna pruriens).

Electrical stimulation at distinct peripheral sites in spinal nerve injured rats leads to different afferent activation profiles.

The neurophysiological basis by which neuromodulatory techniques lead to relief of neuropathic pain remains unclear. We investigated whether electrical stimulation at different peripheral sites induces unique profiles of A-fiber afferent activation in nerve-injured rats. At 4-6weeks after subjecting rats to L5 spinal nerve injury (SNL) or sham operation, we recorded the orthodromic compound action potential (AP) at the ipsilateral L4 dorsal root in response to (1) transcutaneous electrical nerve stimulation (TENS, a patch electrode placed on the dorsum of the foot), (2) subcutaneous electrical stimulation (SQS, electrode inserted subcutaneously along the dorsum of the foot), (3) peroneal nerve stimulation (PNS, electrode placed longitudinally abutting the nerve), and (4) sciatic nerve stimulation (SNS).

Cross-sectional and longitudinal assessment of aortic root dilation and valvular anomalies in hypermobile and classic Ehlers-Danlos syndrome.

Objectives: To delineate the prevalence of cardiac findings in hypermobile and classic Ehlers-Danlos syndrome and provide longitudinal analysis of aortic root growth.

Study Design: A retrospective chart review was conducted, and data were analyzed for cross-sectional prevalence of aortic dilation and valvular anomalies. The clinical implications of aortic root growth were determined by assessment of progression of aortic root measurements over time and clinical symptoms.

Spinal cord stimulation-induced analgesia: electrical stimulation of dorsal column and dorsal roots attenuates dorsal horn neuronal excitability in neuropathic rats.

Background: The sites of action and cellular mechanisms by which spinal cord stimulation reduces neuropathic pain remain unclear.

Methods: We examined the effect of bipolar electrical-conditioning stimulation (50 Hz, 0.2 ms, 5 min) of the dorsal column and lumbar dorsal roots on the response properties of spinal wide dynamic range (WDR) neurons in rats after L5 spinal nerve injury.

A role for acid-sensing ion channel 3, but not acid-sensing ion channel 2, in sensing dynamic mechanical stimuli.

Background: Acid-sensing ion channels 2 and 3 (ASIC2 and ASIC3, respectively) have been implicated as putative mechanotransducers. Because mechanical hyperalgesia is a prominent consequence of nerve injury, we tested whether male and female ASIC2 or ASIC3 knockout mice have altered responses to mechanical and heat stimuli at baseline and during the 5 weeks after spinal nerve ligation.

Methods: Age-matched, adult male and female ASIC2 knockout (n=21) and wild-type (WT; n=24) mice or ASIC3 knockout (n=20) and WT (n=19) mice were tested for sensitivity to natural stimuli before and after spinal nerve ligation surgery.

Conduction properties distinguish unmyelinated sympathetic efferent fibers and unmyelinated primary afferent fibers in the monkey.

Background: Different classes of unmyelinated nerve fibers appear to exhibit distinct conductive properties. We sought a criterion based on conduction properties for distinguishing sympathetic efferents and unmyelinated, primary afferents in peripheral nerves.

Methodology/principal Findings: In anesthetized monkey, centrifugal or centripetal recordings were made from single unmyelinated nerve fibers in the peroneal or sural nerve, and electrical stimuli were applied to either the sciatic nerve or the cutaneous nerve endings, respectively.

Effects of soy diet on inflammation-induced primary and secondary hyperalgesia in rat.

Soy consumption is said to prevent or treat atherosclerosis, cancer, pain, and memory deficits, but experimental and clinical evidence to support these claims are lacking. We used in vivo models of inflammation to determine whether a soy diet reduces primary or secondary hyperalgesia. In all three experiments, rats were fed either a soy- or casein-based diet for at least 2 weeks before induction of inflammation and for the duration of experiments.

A role for uninjured afferents in neuropathic pain.

Diseases and injuries to the nervous system can lead to a devastating chronic pain condition called neuropathic pain. We review changes that occur in the peripheral nervous system that may play a role in this disease. Common animal models for neuropathic pain involve an injury to one or more peripheral nerves.

A role for polymodal C-fiber afferents in nonhistaminergic itch.

Recent psychophysical and electrophysiological studies in humans suggest the existence of two peripheral pathways for itch, one that is responsive to histamine and a second pathway that can be activated by nonhistaminergic pruritogens (e.g., cowhage spicules).

Peripherally acting mu-opioid receptor agonist attenuates neuropathic pain in rats after L5 spinal nerve injury.

Studies in experimental models and controlled patient trials indicate that opioids are effective in managing neuropathic pain. However, side effects secondary to their central nervous system actions present barriers to their clinical use. Therefore, we examined whether activation of the peripheral mu-opioid receptors (MORs) could effectively alleviate neuropathic pain in rats after L5 spinal nerve ligation (SNL).

The tibial neuroma transposition (TNT) model of neuroma pain and hyperalgesia.

Peripheral nerve injury may lead to the formation of a painful neuroma. In patients, palpating the tissue overlying a neuroma evokes paraesthesias/dysaesthesias in the distribution of the injured nerve. Previous animal models of neuropathic pain have focused on the mechanical hyperalgesia and allodynia that develops at a location distant from the site of injury and not on the pain from direct stimulation of the neuroma.

Lumbar sympathectomy attenuates cold allodynia but not mechanical allodynia and hyperalgesia in rats with spared nerve injury.

Unlabelled: In certain patients with neuropathic pain, the pain is dependent on activity in the sympathetic nervous system. To investigate whether the spared nerve injury model (SNI) produced by injury to the tibial and common peroneal nerves and leaving the sural nerve intact is a model for sympathetically maintained pain, we measured the effects of surgical sympathectomy on the resulting mechanical allodynia, mechanical hyperalgesia, and cold allodynia. Decreases of paw withdrawal thresholds to von Frey filament stimuli and increases in duration of paw withdrawal to pinprick or acetone stimuli were observed in the ipsilateral paw after SNI, compared with their pre-SNI baselines.

Psychophysical and physiological evidence for parallel afferent pathways mediating the sensation of itch.

The neuronal pathways for itch have been characterized mainly based on responses to histamine. Intracutaneous application of histamine produces intense itch and a large area of axon-reflexive vasodilation ("flare") around the application site. Both phenomena are thought to be mediated through neuronal activity in itch-specific, mechanoinsensitive C-fiber afferents (CMi).

Activity-dependent slowing of conduction velocity in uninjured L4 C fibers increases after an L5 spinal nerve injury in the rat.

Growing evidence suggests that uninjured afferents may play an important role in neuropathic pain following nerve injury. The excitability of nociceptive neurons in the L4 spinal nerve appears to be enhanced following an injury to the adjacent L5 spinal nerve. In this study, we investigated whether the action-potential conduction properties of unlesioned, unmyelinated fibers are also altered.

Mechanisms of neuropathic pain.

Neuropathic pain refers to pain that originates from pathology of the nervous system. Diabetes, infection (herpes zoster), nerve compression, nerve trauma, "channelopathies," and autoimmune disease are examples of diseases that may cause neuropathic pain. The development of both animal models and newer pharmacological strategies has led to an explosion of interest in the underlying mechanisms.

Reversible cardiomyopathy after severe burn injury.

Cardiomyopathy can result in significant morbidity and mortality, leading to long-term cardiac disability or consideration for transplantation. This study reviewed our experience with pediatric burn patients who developed cardiomyopathy during their acute hospitalization. We identified five patients admitted from 1991 to 2003 who were diagnosed with cardiomyopathy during their initial hospitalization and retrospectively collected data regarding hospital course, cardiac dysfunction, radiographic and echocardiographic studies, pharmacologic treatment, and long-term cardiac function.

Windup in dorsal horn neurons is modulated by endogenous spinal mu-opioid mechanisms.

The mu-opioid receptor (MOR) plays a critical role in morphine analgesia and nociceptive transmission. However, the physiological roles for endogenous MOR mechanisms in modulating spinal nociceptive transmission, and particularly in the enhanced excitability of spinal nociceptive neurons after repeated noxious inputs, are less well understood. Using a MOR gene knock-out (-/-) approach and an MOR-preferring antagonist, we investigated the roles of endogenous MOR mechanisms in processing of acute noxious input and in neuronal sensitization during windup-inducing stimuli in wide dynamic range (WDR) neurons.

C-fiber (Remak) bundles contain both isolectin B4-binding and calcitonin gene-related peptide-positive axons.

Unmyelinated nerve fibers (Remak bundles) in the rodent sciatic nerve typically contain multiple axons. This study asked whether C-fiber bundles contain axons arising from more than one type of neuron. Most small neurons of the lumbar dorsal root ganglion (DRG) are either glial cell line-derived neurotrophic factor dependent or nerve growth factor dependent, binding either isolectin B4 (IB4) or antibodies to calcitonin gene-related peptide (CGRP), respectively.

Tart cherry anthocyanins suppress inflammation-induced pain behavior in rat.

The use of complementary and alternative medicine (CAM) has increased in the United States and more patients are seeking CAM therapies for control of pain. The present investigation tested the efficacy of orally administered anthocyanins extracted from tart cherries on inflammation-induced pain behavior in rats. Paw withdrawal latency to radiant heat and paw withdrawal threshold to von Frey probes were measured.

The population response of A- and C-fiber nociceptors in monkey encodes high-intensity mechanical stimuli.

The peripheral neural mechanism of pain to mechanical stimuli remains elusive. C-fiber nociceptors do not appear to play a major role in mechanical pain sensation, because the stimulus-response function of mechanically sensitive C-fiber nociceptors to punctate mechanical stimuli applied to the most sensitive region in the receptive field (the hot spot) reaches a plateau at force levels insufficient to produce pain in humans. However, studies at the hot spot give an incomplete understanding of the inputs of nociceptors to the spinal cord.