Single intrathecal administration of the transcription factor decoy AYX1 prevents acute and chronic pain after incisional, inflammatory, or neuropathic injury

Mamet, Julien; Klukinov, Michael; Yaksh, Tony L.; Malkmus, Shelle; Williams, Samantha; Harris, Scott M.; Manning, Donald C.; Taylor, Bradley K.; Donahue, Renée R.; Porreca, Frank; Xie, Jennifer Y.; Oyarzo, Janice; Brennan, Timothy J.; Subieta, Alberto; Schmidt, William K.; Yeomans, David C.

doi:10.1016/j.pain.2013.10.015

Cited by 38 publications

(51 citation statements)

References 33 publications

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“…In the current study, single prolonged stress (SPS) was employed to further analyze these effects on PTSD192021. Complete Freund’s adjuvant (CFA) injection was used to promote chronic inflammatory pain22. Minocycline was used to inactivate microglia and c -fos antisense oligodeoxynucleotides (ASO) was used to disable activated neurons2324.…”

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confidence: 99%

Crosstalk between Activated Microglia and Neurons in the Spinal Dorsal Horn Contributes to Stress-induced Hyperalgesia

Chen

Meng

et al. 2016

Sci Rep

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Stress has been shown to enhance pain sensitivity resulting in stress-induced hyperalgesia. However, the underlying mechanisms have yet to be elucidated. Using single-prolonged stress combined with Complete Freund’s Adjuvant injection model, we explored the reciprocal regulatory relationship between neurons and microglia, which is critical for the maintenance of posttraumatic stress disorder (PTSD)-induced hyperalgesia. In our assay, significant mechanical allodynia was observed. Additionally, activated neurons in spinal dorsal horn were observed by analysis of Fos expression. And, microglia were also significantly activated with the presence of increased Iba-1 expression. Intrathecal administration of c-fos antisense oligodeoxynucleotides (ASO) or minocycline (a specific microglia inhibitor) attenuated mechanical allodynia. Moreover, intrathecal administration of c-fos ASO significantly suppressed the activation of neurons and microglia. Interestingly, inhibition of microglia activation by minocycline significantly suppressed the activation of both neurons and microglia in spinal dorsal horn. P38 inhibitor SB203580 suppressed IL-6 production, and inhibition of IL-6 receptor (IL-6R) activation by tocilizumab suppressed Fos expression. Together, our data suggest that the presence of a “crosstalk” between activated microglia and neurons in the spinal dorsal horn, which might contribute to the stress-induced hyperactivated state, leading to an increased pain sensitivity.

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confidence: 99%

Crosstalk between Activated Microglia and Neurons in the Spinal Dorsal Horn Contributes to Stress-induced Hyperalgesia

Chen

Meng

et al. 2016

Sci Rep

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“…23 More recently, preclinical investigations of the DNA transcription factor decoy, AYX1, demonstrated improved weight-bearing and spontaneous rearing in a rat knee surgery model. 24 The strengths of our study design are that it was a comprehensive comparison between a triple nonopioid analgesic combination and all three of its respective double-drug combinations included a systematic assessment of pain at rest as well as pain evoked by movement. However, this study is also limited by incomplete recruitment as well as concomitant patient-controlled opioid administration, which may equalise appreciable differences in efficacy of the four studied treatment groups.…”

Section: Discussionmentioning

confidence: 99%

The effect of triple vs. double nonopioid therapy on postoperative pain and functional outcome after abdominal hysterectomy

Gilron

Dumerton-Shore

et al. 2015

European Journal of Anaesthesiology

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“…Recent studies have shown that there is activation of peripheral and central gliocytes complicated with release of inflammatory cytokines in neuropathic pain. This uncovered important mechanism for the pathogenesis of neuropathic pain and the accompanied symptoms [19][20][21][22], and it also revealed an important therapeutic target for the treatment of neuropathic pain [23][24][25].…”

Section: Cell Biochem Biophysmentioning

confidence: 92%

The Study of Different Approaches of Parecoxib Sodium Pretreatment on the Behavior of Rats with Neuropathic Pain

Cui

Xue

Zhang

2015

Cell Biochem Biophys

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Our objective is to analyze and observe the different administration routes of parecoxib sodium pretreatment on the behavioral improvement of rats with neuropathic pain to provide the preclinical data of parecoxib sodium on neuropathic pain treatment. 30 SD rats were randomly divided into five groups, including model group, sham operation group, intrathecal injection group (IT group), intraperitoneal injection group (IP group), and perineural infiltration group (PI group). The rats in model group and three parecoxib sodium pretreatment groups received spinal nerve ligation (SNL). Heat pain test and 50 % paw mechanical withdrawal threshold test (50 % PMWT) were use to assess the responses after parecoxib sodium pretreatment. 50 % PMWT results of right foot in five groups had no statistical difference (P > 0.05); 50 % PMWT results of left and right feet in three parecoxib sodium pretreatment groups were obviously higher than SNL group at different time points, which was statistically different (P < 0.05); in comparison with three pretreatment groups, the data of left foot in IT group were obviously higher than PI group and IP group, and the comparison among three groups had significant difference (P < 0.05). However, the data of right foot had no significant difference among three groups (P > 0.05). Paw thermal withdrawal latency (PTWL) results of left and right feet in five groups had no significant difference before surgery (P > 0.05); after the establishment of neuropathic model, PTWL results in five groups were significantly decreased; however, PTWL results of left and right feet at 3 days after surgery in IT group were significantly higher than the two other pretreatment groups (P < 0.05); PTWL results of left and right feet at 7 and 14 days after surgery had no significant difference. Parecoxib sodium pretreatment can effectively improve the behaviors caused by neuropathic pain, and intrathecal injection is the most effective route of administration.

show abstract

Single intrathecal administration of the transcription factor decoy AYX1 prevents acute and chronic pain after incisional, inflammatory, or neuropathic injury

Cited by 38 publications

References 33 publications

Crosstalk between Activated Microglia and Neurons in the Spinal Dorsal Horn Contributes to Stress-induced Hyperalgesia

Crosstalk between Activated Microglia and Neurons in the Spinal Dorsal Horn Contributes to Stress-induced Hyperalgesia

The effect of triple vs. double nonopioid therapy on postoperative pain and functional outcome after abdominal hysterectomy

The Study of Different Approaches of Parecoxib Sodium Pretreatment on the Behavior of Rats with Neuropathic Pain

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