The effect of serotonin–noradrenaline reuptake inhibitor duloxetine on the intervertebral disk-related radiculopathy in rats

Handa, Junichi; Sekiguchi, Miho; Krupková, Olga; Konno, Satoshi

doi:10.1007/s00586-015-4239-9

Cited by 21 publications

(9 citation statements)

References 55 publications

(75 reference statements)

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“…The authors emphatically indicated that duloxetine might be effective in patients with persistent, NSAID‐resistant neuropathic OA pain, and it might diminish the number of patients requiring joint replacement surgery in the future . In addition, duloxetine improved the sensitivity to non‐noxious mechanical stimuli measured by a pain behavioral test in the intervertebral disc‐related radiculopathy model in rats, which is truly regarded as a model for neuropathic pain . With regard to clinical results, several studies conducted in the United States, Europe, and Asia have shown significant improvements in pain, joint junction and function, and health‐related quality of life for patients with hip or knee OA who were treated with duloxetine compared with placebo without serious adverse events .…”

Section: Discussionsupporting

confidence: 52%

“…In a mouse model of diabetic neuropathy, the peripheral and central neuroprotective effects of duloxetine in neuropathic pain were, at least in part, related to its downregulation in the spinal astrocytes and microglia . In another study, the occurrence of activated microglia labeled with Iba1 was tested in a disc‐related radiculopathy model in rats and duloxetine‐inhibited microglia activation . Duloxetine is classified as an SNRI that influences the descending pain modulatory system; therefore, it is assumed that duloxetine dampens pain via the descending pain modulatory system, and this may affect the expression of either Iba1 or microglial chemotaxis from different areas.…”

Section: Discussionmentioning

confidence: 99%

“…Forth, the present study examined only a single administration of duloxetine with a short observation period. Given a previous study reported decreased tumor necrosis factor expression in DRG after administration of duloxetine for consecutive 10 days, downregulation of inflammatory mediators may require longer exposure times . Therefore the further study about daily administration of duloxetine with long observation period is needed to verify the influence on sensory innervation in DRG.…”

Section: Discussionmentioning

confidence: 99%

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Analgesic Effect of Duloxetine on an Animal Model of Monosodium Iodoacetate‐Induced Hip Osteoarthritis

Kawarai

Orita

Nakamura

et al. 2019

Journal Orthopaedic Research

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We investigated the efficacy of duloxetine on hyperalgesia, histopathological and radiographic findings, pain-related sensory innervation of dorsal-root ganglia (DRG), and spinal changes in a rat model of induced hip osteoarthritis (OA). The right hip joints of male Sprague-Dawley rats (n = 6 rats/group) in the Sham group were injected with 25 μl of sterile saline and 25 μl of sterile saline with 2 mg of monosodium iodoacetate (MIA) were injected to the MIA + Vehicle and MIA + Duloxetine groups. We injected duloxetine 20 mg/kg intraperitoneally in the MIA + Duloxetine group 28 days after injection, whereas rats in the MIA + Vehicle group were injected with 0.5 ml of 20% dimethyl sulfoxide. We assessed hyperalgesia, histopathological changes, immunoreactive (-ir) neurons for calcitonin generelated peptide and activating transcription factor 3 in DRG, and immunoreactive neurons for ionized-calcium-binding adaptor molecule 1 (Iba1) in the dorsal horn of the spinal cord. MIA administration into the hip joint let to mechanical hyperalgesia of the ipsilateral hind paw (p < 0.05). A single injection of duloxetine significantly attenuated it in induced hip OA (p < 0.05) and suppressed the number of Iba1-ir microglia of the ipsilateral dorsal horn (p < 0.05). These results suggest that a single injection of duloxetine suppressed mechanical hyperalgesia and may influence the expression of Iba1 in the microglia of the ipsilateral dorsal horn in the MIA-induced hip OA. This finding implies the inhibitory effects of duloxetine against neuropathic pain, which may lead to a change of microglial activities.

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Section: Discussionsupporting

confidence: 52%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Analgesic Effect of Duloxetine on an Animal Model of Monosodium Iodoacetate‐Induced Hip Osteoarthritis

Kawarai

Orita

Nakamura

et al. 2019

Journal Orthopaedic Research

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“…In contrast, some studies showed that the level of spinal serotonin increased or was not changed after spinal nerve injury [ 25 , 26 ]. Two recent experimental studies have shown that using selective serotonin or serotonin–noradrenaline reuptake inhibitors may be associated with reduction of neuropathic pain related to lumbar disk herniation and inhibition of tumor necrosis factor expression after two or three weeks of treatment suggesting the pronociceptive feature of serotonin in lumbar disk herniation-related pain [ 27 , 28 ]. On the other hand, in a systematic review by Urquhart et al, in 2008, including nine randomized controlled trials, no significant relief in chronic low back pain was observed in patients who were treated with SSRIs [ 29 ].…”

Section: Discussionmentioning

confidence: 99%

Association of Serum Serotonin and Pain in Patients with Chronic Low Back Pain before and after Spinal Surgery

Farhanchi

Karkhanei

Amani

et al. 2018

Pain Research and Treatment

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Introduction In this study we are aiming to evaluate the changes of serum serotonin and its association with pain in patients suffering from chronic low back pain before and after lumbar discectomy surgery. Patients and Methods A prospective study was performed on the patients referring to the outpatient clinic in Besat hospital, Hamadan University of Medical Sciences, Hamadan, Iran, during 2016. A 2 mL fasting blood sample was collected from each patient at preoperative day 1 and postoperative day 14 and they were measured for level of serum serotonin. Besides, all patients were asked for severity of their low back pain in preoperative day 1 and postoperative day 14 and scored their pain from zero to ten using a Numerical Rating Scale. Results Forty patients with the mean age of 47 ± 13 yrs/old (range 25–77) including 15 (37.5%) males were enrolled into the study. The overall mean score of preoperative pain was significantly decreased from 7.4 ± 2.18 (range 4–10) to the postoperative pain score 3.87 ± 2.92 (range 0–10) (P < .001). The overall levels of pre- and postoperative serum serotonin were 3.37 ± 1.27 (range 1.1–6.4) and 3.58 ± 1.32 (range .94–7.1) ng/mL, respectively, with no significant difference (P = .09). The levels of pre- and postoperative serum serotonin were significantly higher in males and patients older than 50 yrs/old compared to the females and patients younger than 50 yrs/old, respectively (P = .03 and .005, respectively). A significant inverse correlation between the postoperative levels of pain and serum serotonin was observed (r = -.36 and P = .02). Conclusion A negative medium strength linear relationship may exist between the postoperative serum serotonin and low back pain.

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“…Inhibition of microglial activation has been recently identified as a new mechanism which strongly contributes to the analgesic effects of duloxetine (Kremer et al, 2018; Tawfik et al, 2018). The first evidence in this regard comes from studies carried out in animal models of chemotherapy-induced neuropathy (Greish et al, 2014) and intervertebral disc-related neuropathic pain (Handa et al, 2016). Furthermore, the inhibition of mechanical allodynia and thermal hyperalgesia induced by duloxetine, in a mouse model of diabetic neuropathy, was paralleled by a significant reduction of specific markers of microglia (CD11b) and astrocyte (GFAP) activation (Tawfik et al, 2018).…”

Section: Rescue Of Noradrenergic System As a Novel Pharmacological Apmentioning

confidence: 99%

Rescue of Noradrenergic System as a Novel Pharmacological Strategy in the Treatment of Chronic Pain: Focus on Microglia Activation

et al. 2019

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Different types of pain can evolve toward a chronic condition characterized by hyperalgesia and allodynia, with an abnormal response to normal or even innocuous stimuli, respectively. A key role in endogenous analgesia is recognized to descending noradrenergic pathways that originate from the locus coeruleus and project to the dorsal horn of the spinal cord. Impairment of this system is associated with pain chronicization. More recently, activation of glial cells, in particular microglia, toward a pro-inflammatory state has also been implicated in the transition from acute to chronic pain. Both α2- and β2-adrenergic receptors are expressed in microglia, and their activation leads to acquisition of an anti-inflammatory phenotype. This review analyses in more detail the interconnection between descending noradrenergic system and neuroinflammation, focusing on drugs that, by rescuing the noradrenergic control, exert also an anti-inflammatory effect, ultimately leading to analgesia. More specifically, the potential efficacy in the treatment of neuropathic pain of different drugs will be analyzed. On one side, drugs acting as inhibitors of the reuptake of serotonin and noradrenaline, such as duloxetine and venlafaxine, and on the other, tapentadol, inhibitor of the reuptake of noradrenaline, and agonist of the µ-opioid receptor.

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The effect of serotonin–noradrenaline reuptake inhibitor duloxetine on the intervertebral disk-related radiculopathy in rats

Abstract: SNRI duloxetine inhibited neuropathic pain in rats possibly via down-regulating TNF, NGF, and microglia activation. We conclude that duloxetine, and most likely other SNRIs, may be used for the management of lumbar neuropathic pain.

Cited by 21 publications

References 55 publications

Analgesic Effect of Duloxetine on an Animal Model of Monosodium Iodoacetate‐Induced Hip Osteoarthritis

Analgesic Effect of Duloxetine on an Animal Model of Monosodium Iodoacetate‐Induced Hip Osteoarthritis

Association of Serum Serotonin and Pain in Patients with Chronic Low Back Pain before and after Spinal Surgery

Rescue of Noradrenergic System as a Novel Pharmacological Strategy in the Treatment of Chronic Pain: Focus on Microglia Activation

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