Influence of TRPV1 on Diabetes-Induced Alterations in Thermal Pain Sensitivity

Abstract

A common complication associated with diabetes is painful or painless diabetic peripheral neuropathy (DPN). The mechanisms and determinants responsible for these peripheral neuropathies are poorly understood. Using both streptozotocin (STZ)-induced and transgene-mediated murine models of type 1 diabetes (T1D), we demonstrate that Transient Receptor Potential Vanilloid 1 (TRPV1) expression varies with the neuropathic phenotype. We have found that both STZ- and transgene-mediated T1D are associated with two distinct phases of thermal pain sensitivity that parallel changes in TRPV1 as determined by paw withdrawal latency (PWL). An early phase of hyperalgesia and a late phase of hypoalgesia are evident. TRPV1-mediated whole cell currents are larger and smaller in dorsal root ganglion (DRG) neurons collected from hyperalgesic and hypoalgesic mice. Resiniferatoxin (RTX) binding, a measure of TRPV1 expression is increased and decreased in DRG and paw skin of hyperalgesic and hypoalgesic mice, respectively. Immunohistochemical labeling of spinal cord lamina I and II, dorsal root ganglion (DRG), and paw skin from hyperalgesic and hypoalgesic mice reveal increased and decreased TRPV1 expression, respectively. A role for TRPV1 in thermal DPN is further suggested by the failure of STZ treatment to influence thermal nociception in TRPV1 deficient mice. These findings demonstrate that altered TRPV1 expression and function contribute to diabetes-induced changes in thermal perception.

Electroacupuncture counteracts the development of thermal hyperalgesia and the alteration of nerve growth factor and sensory neuromodulators induced by streptozotocin in adult rats

“…Our present data do not allow further speculation on this issue. However, since the spinal production of TRPV1 has been correlated with the development of thermal hyperalgesia in diabetic animals [5,29], our data underline the possibility that the efficacy of electroacupuncture in the control of spinal sensitisation during the development of neuropathic pain states could be mediated by the modulation of NGF and TRPV1 levels.…”

“…Painful neuropathy is associated with behavioural manifestations of sensory dysfunctions, and neurochemical alterations of biological mediators in the peripheral nervous system [2]. In particular, alterations in the content of neurotrophin nerve growth factor (NGF) in tissues (skin, muscle and serum) [3] are associated with spinal variations in substance P (SP) [3] and transient receptor potential vanilloid 1 (TRPV1) receptor [4,5]. These latter are known to be under the control of NGF [6][7][8] and have been related to diabetes-induced neuropathy.…”

“…Among others, the streptozotocin-induced type-1 diabetes model in rodents is characterised by early functional abnormalities, including thermal hyperalgesia [5,28], associated with spinal deregulation of TRPV1 [5,29], SP [3] and GABA [25,26].…”

An Inhibitor of Neuronal Exocytosis (DD04107) Displays Long-Lasting In Vivo Activity against Chronic Inflammatory and Neuropathic Pain

“…DD04107 Ameliorated the Mechanical Sensitivity of a Diabetic Neuropathy. We also investigated the effect of the peptide on the mechanical allodynia associated to a diabetes-induced neuropathy (Pabbidi et al, 2008;Suri and Szallasi, 2008). Administration of STZ into mice increases the plasma glucose levels above 250 mg/dl, producing overtime a peripheral neuropathy exhibiting conspicuous mechanical hypersensitivity (Fig.…”

B-type (brain) natriuretic peptide and pruritus in hemodialysis patients

“…10 A recent report suggested that TRPV1 expression is altered in the streptozotocin-induced and transgene-mediated type-1 diabetes mouse model. 31 Thus, it is suggested that pruritus signals were blocked not only by damaged C-fibers, but also by reduced expression of receptors.…”