Minocycline reduces mechanical allodynia and depressive-like behaviour in type-1 diabetes mellitus in the rat

Abstract

A common and devastating complication of diabetes mellitus is painful diabetic neuropathy (PDN) that can be accompanied by emotional disorders such as depression. A few studies have suggested that minocycline that inhibits microglia may attenuate pain hypersensitivity in PDN. Moreover, a recent study reported that minocycline has an acute antidepressive-like effect in diabetic animals. Here we studied whether (i) prolonged minocycline treatment suppresses pain behaviour in PDN, (ii) the minocycline effect varies with submodality of pain, and (iii) the suppression of pain behaviour by prolonged minocycline treatment is associated with antidepressive-like effect. The experiments were performed in streptozotocin-induced rat model of type-1 diabetes. Pain behaviour was evoked by innocuous (monofilaments) and noxious (paw pressure) mechanical stimulation, innocuous cold (acetone drops) and noxious heat (radiant heat). Depression-like behaviour was assessed using forced swimming test. Minocycline treatment (daily 80mg/kg per os) of three-week duration started four weeks after induction of diabetes. Diabetes induced mechanical allodynia and hyperalgesia, cold allodynia, heat hypoalgesia, and depression-like behaviour. Minocycline treatment significantly attenuated mechanical allodynia and depression-like behaviour, while it failed to produce significant changes in mechanical hyperalgesia, cold allodynia or heat hypoalgesia. The results indicate that prolonged per oral treatment with minocycline has a sustained mechanical antiallodynic and antidepressive-like effect in PDN. These results support the proposal that minocycline might provide a treatment option for attenuating sensory and comorbid emotional symptoms in chronic PDN.

Depression‐related behavioural and neuroendocrine changes in the Spontaneously Diabetic Torii (SDT) fatty rat, an animal model of type 2 diabetes mellitus

“…Several studies have suggested a relationship between DM and psychiatric deficits, demonstrated by increased immobility time in the FST in STZ‐diabetic mice, and decreased time spent in an open arm in the elevated plus maze test (anxiety‐like behaviour) . More recently, another study demonstrated that rats with diabetes induced by a combination of high fat diet and STZ exhibit various depression‐like behavioural deficits, such as decreased sucrose preference and increased latency to feeding in the novelty suppression of feeding test .…”

“…For example, streptozotocin (STZ)-induced diabetic mice were reported to show longer periods of immobility in forced swimming tests (FST), suggesting depression-like behaviour. 7,8 In addition, STZ-diabetic rats exhibit an abnormal stress response, characterised by the excessive secretion of corticosterone when exposed to acute stress; this abnormal stress response is frequently observed in depressed patients, suggesting hyperactivation of the hypothalamic-pituitary-adrenal (HPA) axis. 9 Moreover, recent studies have revealed biochemical changes in the brains of animal models of DM.…”

Assessing the Effects of Parthenolide on Inflammation, Bone Loss, and Glial Cells within a Collagen Antibody-Induced Arthritis Mouse Model

“…Mechanical hypersensitivity was hypothesised to be reduced in PAR-treated mice due to the reduction in glial cells observed, as microglia and astrocytes are associated with neuropathic pain [36,37]. Findings from Lampa et al suggest that nociception from an inflammatory experimental arthritis mouse model was due to changes in both the peripheral and central nervous system [38].…”

An Electroencephalography Bioassay for Preclinical Testing of Analgesic Efficacy

“…In support of our behavioral results, daily minocycline treatment (80 mg/kg once/day, p.o.) for 3 weeks started four weeks after induction of diabetes has been shown to attenuate mechanical allodynia while failing to produce significant changes in PWL in a rat model of peripheral diabetic neuropathy 22 . Importantly, it has also been shown that PWL and mechanical allodynia are attenuated when minocycline is administered preemptively prior to CCI (up to 40 mg/kg, i.p.…”

“…However, prolonged treatment with minocycline (p.o.) at 80 mg/kg has been shown to reverse mechanical allodynia in a rat model of painful diabetic neuropathy 22 , 23 . Moreover, the analgesic efficacy of minocycline in human studies is inconclusive, even at relatively high doses 24 – 27 .…”