Hyperalgesia In Diabetic Rats Is Alleviated By A Prosaposin‐Derived Peptide

Abstract

The saposin C‐derived peptide TX14(A) prevents onset of functional and structural disorders in the peripheral nerve of diabetic rats. We have now investigated the ability of TX14(A) to alleviate behavioral indices of abnormal pain perception in adult female rats 4‐6 weeks after onset of STZ‐induced diabetes. Untreated diabetic rats exhibited tactile allodynia (response threshold = 3 ± 1 g) compared to age‐matched controls (10 ± 1g). A single ip injection of TX14(A) transiently alleviated tactile allodynia, with an effect that was maximal 6 hours (11 ± 1g) after injection and diminished within 48 hours. Maximal efficacy was seen with a 1 mg/kg dose while no effects were noted in control rats. Control rats exhibited a transient thermal hyperalgesia (77 ± 5% of baseline paw withdrawal latency) 15 minutes after intrathecal delivery of substance P (30 nmol) that resolved within 30 minutes. Untreated diabetic rats exhibited substance P evoked thermal hyperalgesia of similar magnitude (82 ± 5% at 15 minutes) but of greater duration (83 ± 4% at 1 hour). Intrathecal delivery of TX14(A) 30 minutes before intrathecal substance P was without effect on the transient thermal hyperalgesia in control rats (74 ± 9% at 15 minutes). In diabetic rats, the prolonged thermal hyperalgesia was abolished by prior intrathecal delivery of TX14(A), although the transient thermal hyperalgesia (72 ± 8% at 15 minutes) remained. These studies show that TX14(A) can rapidly allevate diabetes‐induced allodynia and hyperalgesia for up to 48 hours.