Pregnancy suppresses neuropathic pain induced by chronic constriction injury in rats through the inhibition of TNF-&amp;alpha;

Onodera, Yoshiko; Kanao-Kanda, Megumi; Kanda, Hirotsugu; Sasakawa, Tomoki; Iwasaki, Hiroshi; Kunisawa, Takayuki

doi:10.2147/jpr.s121810

Cited by 8 publications

(6 citation statements)

References 45 publications

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“…TNF-α is the most common and important proinflammatory factor that mediates pain, especially neuropathic pain, which prompts leukocyte transmigration into the nerves. 14 , 22 IL-6 is an emerging regulator of pathological pain; a variety of pain models has shown elevated expression levels of IL-6 in the spinal cord and dorsal root ganglia. Besides, the administration of IL-6 protein can result in mechanical allodynia and thermal hyperalgesia.…”

Section: Discussionmentioning

confidence: 99%

“…A series of experiments have proven that late-pregnant mice exhibit efficient resistance to mechanical, thermal and visceral pain, indicating a condition of PIA. 1 , 8 , 13 , 14 , 26 The increase in the nociceptive threshold in the late stage of gestation is beneficial for the mother. Previous studies have shown the effect of maternal antinociception on central and peripheral processing.…”

Section: Discussionmentioning

confidence: 99%

“… 13 Evidence has shown that pregnancy reduces the level of tumor necrosis factor-α (TNF-α) to reduce neuropathic pain in rats with chronic constriction injury (CCI). 14 However, the detailed immunosuppressive molecular mechanisms underlying PIA have not been investigated.…”

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confidence: 99%

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The Programmed Cell Death Ligand-1/Programmed Cell Death-1 Pathway Mediates Pregnancy-Induced Analgesia via Regulating Spinal Inflammatory Cytokines

Tan

Ding

Zhang³

et al. 2021

Anesthesia &Amp; Analgesia

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BACKGROUND: The maternal pain threshold gradually increases during pregnancy, especially in late pregnancy. A series of mechanisms underlying pregnancy-induced analgesia have been reported. However, these mechanisms are still not completely clear, and the underlying molecular mechanisms need further investigation. We examined the relationship between the antinociceptive effect and the expression level of programmed cell death ligand-1 (PD-L1) during pregnancy and further observed the changes in pain thresholds and expression levels of cytokines in late-pregnant mice before and after blockade of PD-L1 or programmed cell death-1 (PD-1). METHODS: Part 1: Female mice were assigned to 3 groups (nonpregnant, late-pregnant, and postpartum). Part 2: Late-pregnant mice were assigned to 3 treatment groups (control [phosphate buffer solution], RMP1-14 [mouse anti–PD-1 antibody], and soluble PD-1 [sPD-1]). Behavioral testing (mechanical and thermal) and tissue (serum and spinal cord) analysis were performed on all groups. PD-L1, interleukin (IL)-10, tumor necrosis factor-α (TNF-α), and IL-6 expression levels in tissue were examined via reverse transcription-polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay (ELISA), and Western blot analysis. RESULTS: The mechanical and thermal pain thresholds were significantly increased in late pregnancy and decreased after delivery. PD-L1 expression was also elevated in late pregnancy and decreased after delivery. In addition, in the late stage of gestation, the maternal inflammatory microenvironment was dominated by anti-inflammatory factors. After administration of RMP1-14 or sPD-1, the pain thresholds of late-pregnant mice were significantly reduced. In late-pregnant mice, the high level of IL-10 was obviously reduced, and the low levels of TNF-α and IL-6 were elevated. CONCLUSIONS: The PD-L1/PD-1 pathway mediates pregnancy-induced analgesia, partially via the regulation of cytokines.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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The Programmed Cell Death Ligand-1/Programmed Cell Death-1 Pathway Mediates Pregnancy-Induced Analgesia via Regulating Spinal Inflammatory Cytokines

Tan

Ding

Zhang³

et al. 2021

Anesthesia &Amp; Analgesia

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“… 21 As a specific marker for astrocytes, GFAP is often used for the detection of astrocytes. During the development of NP, activated astrocytes could release increased amount of GFAP, which might be associated with hyperalgesia and allodynia, 22 and also the maintenance of chronic pain. In this study, the activation of astrocytes occurred in the early stage of CCI, reached the peak until 7 days, and maintained to 14 days after surgery.…”

Section: Discussionmentioning

confidence: 99%

The analgesic effect of early hyperbaric oxygen treatment in chronic constriction injury rats and its influence on nNOS and iNOS expression and inflammatory factor production

et al. 2018

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ObjectiveTo observe the analgesic effect of early hyperbaric oxygen (HBO) treatment in chronic constriction injury (CCI) rats, and to analyze the influence of HBO on the expression of neuronal nitric oxide synthase and inducible nitric oxide synthase and on the levels of inflammatory factors.MethodsRats were assigned into three groups randomly: sham, CCI, and HBO groups. The CCI rat model was established, and HBO treatment at 2.5 ATA (60 min) was given one day after surgery, lasting for five consecutive days. The pain behaviors of the rats were observed at predetermined time points, and the activation of astrocytes at dorsal horns as well as the changes of the synaptic ultrastructures were observed. The expressions of inducible nitric oxide synthase and neuronal nitric oxide synthase were detected by Western blot, and the levels of tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β) were detected by quantitative real-time PCR.ResultsRats in the CCI group developed hyperalgesia when compared with the sham group. Mechanical withdrawal threshold decreased and thermal withdrawal latency shortened in CCI group. Also, astrocytes at the dorsal horn were activated, the synaptic structure was disordered, the expressions of inducible nitric oxide synthase and neuronal nitric oxide synthase were increased significantly, and the release of inflammatory factor (TNF-α and IL-1β) was up-regulated. However, with early initiation of HBO treatment, rats in the HBO group showed significantly alleviated hyperalgesia, increased mechanical withdrawal threshold, and prolonged thermal withdrawal latency. HBO treatment inhibited astrocyte expression and maintained normal synaptic structure. The expressions of inducible nitric oxide synthase and neuronal nitric oxide synthase were decreased in the dorsal horn, and the release of inflammatory factor (TNF-α and IL-1β) was reduced.ConclusionsEarly HBO treatment significantly improves hyperalgesia in rats with neuropathic pain. The decreased expressions of inducible nitric oxide synthase and neuronal nitric oxide synthase and reduced levels of inflammatory factors are important mechanisms by which early HBO helps to alleviate neuropathic pain.

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“…More recently, others have found that pregnancy could reduce the pain hypersensitivity produced in the chronic constriction injury model, in which the sciatic nerve is constricted partially with ligature, 40 during late pregnancy in rats. 41 Of note, T cells have been found to be involved critically in pain processing in female but not in male mice, whereas glial cells are critical to pain transmission in male but not in female mice. 15 During pregnancy, the dampening of the immune system to protect the fetus 42 may explain some pregnancy-induced analgesia.…”

Section: Pain and Pregnancymentioning

confidence: 99%

The Need to Consider Pregnancy As a Biological Variable to Reduce Preventable Suffering Related to Pregnancy

Thomas

Bruckheim

White

2021

Journal of Women's Health

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Maternal morbidity and mortality constitute a national health crisis, and pain is a significant component of maternal morbidity. One important way to reduce maternal morbidity is to reduce the pain associated with pregnancy. Unfortunately, our understanding of how to reduce pain in women is hampered because, historically, mostly male subjects have been used in the study of pain. However, more recently, females increasingly have been included in pain research studies, and astounding differences in how males and females process pain have been uncovered. Moreover, pain in nonpregnant women differs in many ways from pain experienced by pregnant women. We argue here that to better address maternal morbidity, we must better address the pain associated with pregnancy. Furthermore, just as it is important to include both men and women in pain research to better understand pain in both sexes, conducting pain research in pregnant women is essential to finding ways to reduce pain in pregnant women.

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Pregnancy suppresses neuropathic pain induced by chronic constriction injury in rats through the inhibition of TNF-α

Cited by 8 publications

References 45 publications

The Programmed Cell Death Ligand-1/Programmed Cell Death-1 Pathway Mediates Pregnancy-Induced Analgesia via Regulating Spinal Inflammatory Cytokines

The Programmed Cell Death Ligand-1/Programmed Cell Death-1 Pathway Mediates Pregnancy-Induced Analgesia via Regulating Spinal Inflammatory Cytokines

The analgesic effect of early hyperbaric oxygen treatment in chronic constriction injury rats and its influence on nNOS and iNOS expression and inflammatory factor production

The Need to Consider Pregnancy As a Biological Variable to Reduce Preventable Suffering Related to Pregnancy

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