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Abstracts of the 8th Meeting of the Italian Peripheral Nerve Study Group: 21
Author(s) -
Bianchi R,
Savino C,
Cavaletti G,
Oggioni N,
Lauria G,
Borgna M,
Ghezzi P,
Brines M,
Cerami A
Publication year - 2003
Publication title -
journal of the peripheral nervous system
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1
H-Index - 67
eISSN - 1529-8027
pISSN - 1085-9489
DOI - 10.1046/j.1529-8027.2003.00021.x
Subject(s) - medicine , nerve conduction velocity , peripheral neuropathy , streptozotocin , erythropoietin , therapeutic effect , diabetes mellitus , neuroprotection , hyperalgesia , endocrinology , anesthesia , nociception , receptor
Erythropoietin (EPO) has neurotrophic and neuroprotective effects and its efficacy and safety has been demonstrated in patients with ischemic stroke. We investigated its efficacy in preventing and reversing established nerve disorders in streptozotocin (STZ) diabetes. After STZ injection (60 mg/kg/ip), EPO (5000 units/kg b.w. i.p. three times a week) was started in a group of rats and continued for five weeks (prevention schedule). In another group of diabetic rats, EPO was started six weeks after STZ, continued for five weeks (therapeutic schedule). Groups of non‐diabetic control rats were similarly treated. Antidromic nerve conduction velocity (NCV) in the tail was assessed at five weeks for all groups and at 11 weeks for the therapeutic schedule. Compared to non‐diabetic rats, NCV was 21% lower (P < 0.001) at five weeks in the STZ group, EPO partially prevented this decrease (14% lower than with non‐diabetic controls), with a significant difference from the untreated‐diabetic group (P < 0.01). After six weeks of uncontrolled diabetes, at the beginning of therapeutic EPO, NCV was reduced by 23% and after 11 weeks by 40%, EPO efficacy was confirmed. Thermal (hot plate method) and mechanical (Randall‐Selitto method) nociceptive thresholds were monitored weekly throughout the study. In addition, in all groups, the density of intra‐epidermal nerve fibers, which reflects possible degeneration of somatic unmyelinated fibers, was assessed in the hindpaw using protein‐gene‐product 9.5 immunostaining. Rats developed mechanical hyperalgesia within two weeks after STZ injection. Both the prevention and therapeutic schedules of EPO reduced diabetic hyperalgesia after two weeks of treatment, reaching statistical significance at fur, and five weeks of treatment, with no such effect in non‐diabetic controls. Hindpaw thermal response latencies were significantly (P < 0.001) increased in untreated diabetic rats compared with untreated controls. EPO had no effect on these latencies in control rats but partially prevented the increase in diabetic rats, so the values were still different from controls, but significantly different from untreated diabetics at four and five weeks in both the prevention and therapeutic studies (P < 0.05). These observations extend the therapeutic utility of EPO and highlight its potential for treating established diabetic neuropathies.