TY - JOUR
T1 - Diabetic neuropathic pain
T2 - A role for testosterone metabolites
AU - Calabrese, Donato
AU - Giatti, Silvia
AU - Romano, Simone
AU - Porretta-Serapiglia, Carla
AU - Bianchi, Roberto
AU - Milanese, Marco
AU - Bonanno, Giambattista
AU - Caruso, Donatella
AU - Viviani, Barbara
AU - Gardoni, Fabrizio
AU - Garcia-Segura, Luis Miguel
AU - Melcangi, Roberto Cosimo
PY - 2014/4
Y1 - 2014/4
N2 - Diabetic neuropathy is associated with neuropathic pain in about 50% of diabetic subjects. Clinical management of neuropathic pain is complex and so far unsatisfactory. In this study, we analyzed the effects of the testosterone metabolites, dihydrotestosterone (DHT), and 3α-diol, on nociceptive and allodynia thresholds and on molecular and functional parameters related to pain modulation in the dorsal horns of the spinal cord and in the dorsal root ganglia of rats rendered diabetic by streptozotocin injection. Furthermore, the levels of DHT and 3α-diol were analyzed in the spinal cord. Diabetes resulted in a significant decrease in DHT levels in the spinal cord that was reverted by DHT or 3α-diol treatments. In addition, 3α-diol treatment resulted in a significant increase in 3α-diol in the spinal cord compared with control values. Both steroids showed analgesic properties on diabetic neuropathic pain, affecting different pain parameters and possibly by different mechanisms of action. Indeed, DHT counteracted the effect of diabetes on the mechanical nociceptive threshold, pre- and post-synaptic components, glutamate release, astrocyte immunoreactivity, and expression of interleukin-1β (IL1β), while 3α-diol was effective on tactile allodynia threshold, glutamate release, astrocyte immunoreactivity and the expression of substance P, toll-like receptor 4, tumor necrosis factor-α, transforming growth factor β-1, IL1β, and translocator protein. These results indicate that testosterone metabolites are potential agents for the treatment of diabetic neuropathic pain.
AB - Diabetic neuropathy is associated with neuropathic pain in about 50% of diabetic subjects. Clinical management of neuropathic pain is complex and so far unsatisfactory. In this study, we analyzed the effects of the testosterone metabolites, dihydrotestosterone (DHT), and 3α-diol, on nociceptive and allodynia thresholds and on molecular and functional parameters related to pain modulation in the dorsal horns of the spinal cord and in the dorsal root ganglia of rats rendered diabetic by streptozotocin injection. Furthermore, the levels of DHT and 3α-diol were analyzed in the spinal cord. Diabetes resulted in a significant decrease in DHT levels in the spinal cord that was reverted by DHT or 3α-diol treatments. In addition, 3α-diol treatment resulted in a significant increase in 3α-diol in the spinal cord compared with control values. Both steroids showed analgesic properties on diabetic neuropathic pain, affecting different pain parameters and possibly by different mechanisms of action. Indeed, DHT counteracted the effect of diabetes on the mechanical nociceptive threshold, pre- and post-synaptic components, glutamate release, astrocyte immunoreactivity, and expression of interleukin-1β (IL1β), while 3α-diol was effective on tactile allodynia threshold, glutamate release, astrocyte immunoreactivity and the expression of substance P, toll-like receptor 4, tumor necrosis factor-α, transforming growth factor β-1, IL1β, and translocator protein. These results indicate that testosterone metabolites are potential agents for the treatment of diabetic neuropathic pain.
KW - Astrocyte immunoreactivity
KW - Cytokines
KW - Diabetic neuropathy
KW - Glutamate
KW - Neuroactive steroids
KW - Streptozotocin
KW - Substance p
KW - Synaptic proteins
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U2 - 10.1530/JOE-13-0541
DO - 10.1530/JOE-13-0541
M3 - Article
C2 - 24424289
AN - SCOPUS:84897824612
VL - 221
SP - 1
EP - 13
JO - Journal of Endocrinology
JF - Journal of Endocrinology
SN - 0022-0795
IS - 1
ER -