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As the epidemics of obesity and diabetes expand, there are more patients with these disorders requiring elective surgery. For surgery on the extremities, peripheral nerve blocks have become a highly favorable anesthetic option when compared with general anesthesia. Peripheral blocks reduce respiratory and cardiac stresses, while potentially mitigating untreated peripheral pain that can foster physiologic conditions that increase risks for general health complications. However, local anesthetics are generally accepted to be a rare but possible cause of nerve damage, and there are no evidence-based recommendations for dosing local anesthetic nerve blocks in patients with diabetes. This is important because anesthesiologists do not want to potentially accelerate peripheral nerve dysfunction in diabetic patients at risk. This translational vignette (i) examines laboratory models of diabetes, (ii) summarizes the pharmacology of perineural adjuvants (epinephrine, clonidine, buprenorphine, midazolam, tramadol, and dexamethasone), and (iii) identifies areas that warrant further research to determine viability of monotherapy or combination therapy for peripheral nerve analgesia in diabetic patients. Conceivably, future translational research regarding peripheral nerve blocks in diabetic patients may logically include study of nontoxic injectable analgesic adjuvants, in combination, to provide desired analgesia, while possibly avoiding peripheral nerve toxicity that diabetic animal models have exhibited when exposed to traditional local anesthetics.

Objective: To report the clinical, electrodiagnostic, and pathologic findings in 3 patients who presented with complex regional pain syndrome as their primary manifestation of peripheral nerve vasculitis., Design: Case series., Setting: Outpatient clinic in a tertiary care academic medical center., Patients: Patient 1 was a 39-year-old woman with a 9-year history of non-length-dependent severe burning pain and swelling in her extremities. Patient 2 was a 67-year-old man with a 2-year history of severe burning pain and swelling in an extremity after a fall. Patient 3 was a 74-year-old man with a 6-month history of severe allodynic pain and atrophy of the right hand after a viral illness, Results: In all 3 cases, clinical and electrodiagnostic testing were suggestive of multiple mononeuropathies. Nerve biopsy either confirmed vasculitis (patient 1) or was suggestive of angiopathy (patients 2 and 3). Immunomodulative therapy led to marked clinical improvement in all 3 cases., Conclusions: To our knowledge, this is the first report demonstrating that the inflammatory nerve injury seen with peripheral nerve vasculitis can result in complex regional pain syndrome. Clinical and electrodiagnostic assessments can help in the identification and management of these patients.

Recent advances in regeneration and pain research have revealed gaps in the understanding of normal C-fiber anatomy. In the rat PNS, C-fiber axons assemble into Remak bundles, but beyond this, features of C-fiber organization are not defined. Systematic sampling and quantitation reveals that Remak bundles exiting from the L5 dorsal root ganglion (DRG) contain large numbers of axons, for example, 56% of unmyelinated axons were in bundles of >20 axons. This is different from distal nerve segments such as the hindpaw plantar nerve where the median number of axons per bundle is 3. The cross-sectional area of unmyelinated axons in dorsal root was homogeneous near the DRG but variability in axonal area increased near the spinal cord (p = 0.00001) and the mean axonal area was unchanged. Unmyelinated axons in peripheral nerve were almost always isolated from one another by Schwann cell processes; however, in dorsal root 7% to 9% of unmyelinated axons were immediately adjacent within pockets containing 2 or more axons. Remak bundles in the distal peripheral nerve clustered with other Remak bundles. We observe that multiple unmyelinated axons are juxtaposed within the C-fiber/Remak bundle and that the close association of afferent axons may have important functional implications.