Impaired Insulin Signaling as a Potential Trigger of Pain in Diabetes and Prediabetes

Abstract

Chronic sensorimotor distal symmetric polyneuropathy (DPN) is a common neurologic complication of diabetes mellitus. Prevalence of DPN approaches 50% in people living with diabetes, and about 10% of these cases are painful neuropathy. 1,2 Like other symptoms of DPN (loss of reflexes or somatic sensations), ''positive'' symptoms (pain and paresthesias) of DPN have symmetrical distribution and distal-toproximal progression. Nocturnal intensification seems to be another general characteristic of pain in DPN. 2 Otherwise, there is a great variety of individual presentations of this syndrome. Pain may be evoked or spontaneous, persistent or intermittent, and chronic, lasting for years or remitting within 1 year of onset. The persistent, spontaneous pain may be described as superficial or deep, dull, aching, cramp-like, burning, or crushing. The intermittent, chronic pain is frequently perceived as electric-like, shooting, or lancinating. Mechanical allodynia (painful perception of normally nonpainful stimuli) and hyperalgesia (exaggerated pain in response to moderately painful mechanical stimuli) are common types of evoked pain. Paresthesias described in some cases 95

Comparison of metabolic and neuropathy profiles of rats with streptozotocin-induced overt and moderate insulinopenia

“…The critical concentrations of plasma insulin required for maintenance of PPT and glucose are in the ranges of 1.5 – 2 ng/ml and 0.5 - 1 ng/ml, respectively (see Fig. 7 for random and (Dobretsov et al, 2007a) for fasting glucose data). The higher tolerance of glucose metabolism to insulinopenia than that of the PNS may derive from a combination of factors.…”

Distal Degenerative Sensory Neuropathy in a Long-Term Type 2 Diabetes Rat Model

“…Calcutt (36) has argued that some of these discrepancies may arise from testing methodology and the duration of diabetes. Dobretsov et al (37) have suggested that hyperalgesia may relate better to impaired insulin signaling than hyperglycemia. In the current study, despite a long-term end point (4 months), pain behavior had not disappeared in favor of simple sensory loss, despite significant but incomplete epidermal denervation.…”

Diabetes Mellitus, Independent of Body Mass Index, Is Associated With a "Higher Success" Rate for Supraclavicular Brachial Plexus Blocks

“…5 In addition, there have been recent reviews in our specialty's symposium journals addressing mechanisms of chronic pain in the setting of diabetes. 6,7 Interestingly, these excellent reviews did not have any specific citations regarding the care of such patients receiving peripheral nerve blocks for surgical anesthesia-analgesia, presumably because such literature is sparse. There is animal evidence that nerve fibers of patients with diabetes may have a higher sensitivity to local anesthetics.…”