5-HT7 receptor activation attenuates thermal hyperalgesia in streptozocin-induced diabetic mice

Levetiracetam synergises with common analgesics in producing antinociception in a mouse model of painful diabetic neuropathy

“…Recent studies have suggested that the antinociception of paracetamol in neuropathic pain is mediated by cannabinoid receptors [25,53]. As it was shown that activation of 5-HT 7 receptor attenuates thermal hyperalgesia in streptozocin-induced diabetic mice [54], paracetamol might achieve analgesia in this pain state through activation of descending serotonergic pathways and spinal 5-HT 7 receptors [55]. Paracetamol blocks spinal hyperalgesia induced by glutamate receptors agonist N-methyl-D-aspartate (NMDA) [56], which could also contribute to its antinociceptive effect since glutamate excitotoxicity has been implicated in diabetic neuropathic pain [34,57].…”

Evaluation of antinociceptive and antioxidant properties of 3-[4-(3-trifluoromethyl-phenyl)-piperazin-1-yl]-dihydrofuran-2-one in mice

“…Conflicting data have been accumulated regarding the nociceptive thresholds, in particular, for thermal stimuli in STZ diabetic model of pain. These differences can be explained, in part, by the kind or intensity of thermal stimuli as well as the duration of diabetes (Obrosova 2009; Ulugol et al 2012). For the above-mentioned reasons, in our study, pain sensitivity tests were performed 21 days after STZ administration to avoid development of hypoalgesia that often occurs during the advanced phase of diabetic process (Ulugol et al 2012) in STZ-diabetic animals with longer term (≥12 weeks) diabetes (Obrosova 2009).…”

“…These differences can be explained, in part, by the kind or intensity of thermal stimuli as well as the duration of diabetes (Obrosova 2009; Ulugol et al 2012). For the above-mentioned reasons, in our study, pain sensitivity tests were performed 21 days after STZ administration to avoid development of hypoalgesia that often occurs during the advanced phase of diabetic process (Ulugol et al 2012) in STZ-diabetic animals with longer term (≥12 weeks) diabetes (Obrosova 2009). Lack of visible degenerative changes in the general structure of the sciatic nerve of diabetic animals at the time point at which we carried out behavioral tests was proven under a light microscope, so the effects observed in behavioral tests (lowering of nociceptive thresholds in baseline measurement and elevation of pain thresholds induced by LPP1) cannot be attributed to STZ-induced hypoalgesia.…”

5-HT7 receptor activation: A novel target for treatment of opioid-induced hyperalgesia – A hypothesis and mini review

“…5,6 When 5-HT7 agonists are administered systemically, the antinociceptive action at the central level seems to be predominant than the pronociceptive action at the peripheral level, and exert antihyperalgesic effects in capsaicin challenge, nerve injury and diabetic neuropathy models. [4][5][6]27 Spinal 5-HT7 receptors mediate the inhibitory effect of descending serotonergic pathways on nociceptive transmission. Suggestion of a pivotal role for 5-HT7 receptors in morphine, tramadol, cannabinoid, paracetamol and amitriptyline-induced antinociception are the supporting evidence for this hypothesis.…”