Early repeated administration of progesterone improves the recovery of neuropathic pain and modulates spinal 18kDa-translocator protein (TSPO) expression

Liu, Xiaoming; Li, Weiyan; Dai, Li-Yang; Zhang, Tingting; Xia, Weiliang; Liu, Hongjun; Ma, Ke; Xu, Jianguo; Jin, Yi

doi:10.1016/j.jsbmb.2014.02.017

Cited by 20 publications

(16 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Direct microinjection of the neurosteroids AP or DOC had similar effects. These results are consistent with previous reports that systemic (intraperitoneal) or intrathecal administration of neurosteroids (PROG or AP) relieve or abolish established pain behaviors [17,48,49]. Intrathecal administration of Ro5-4864, another widely-used TSPO activator, also retards or prevents the development of inflammatory and neuropathic pain [43,44].…”

Section: Up-regulation Of Neurosteroids In the Lateral Thalamus Reliesupporting

confidence: 92%

Elevated Neurosteroids in the Lateral Thalamus Relieve Neuropathic Pain in Rats with Spared Nerve Injury

et al. 2016

View full text Add to dashboard Cite

Neurosteroids are synthesized in the nervous system from cholesterol or steroidal precursors imported from peripheral sources. These compounds are important allosteric modulators of c-aminobutyric acid A receptors (GABA A Rs), which play a vital role in pain modulation in the lateral thalamus, a main gate where somatosensory information enters the cerebral cortex. Using high-performance liquid chromatography/tandem mass spectrometry, we found increased levels of neurosteroids (pregnenolone, progesterone, deoxycorticosterone, allopregnanolone, and tetrahydrodeoxycorticosterone) in the chronic stage of neuropathic pain (28 days after spared nerve injury) in rats.The expression of the translocator protein TSPO, the upstream steroidogenesis rate-limiting enzyme, increased at the same time. In vivo stereotaxic microinjection of neurosteroids or the TSPO activator AC-5216 into the lateral thalamus (AP -3.0 mm, ML ±3.0 mm, DV 6.0 mm) alleviated the mechanical allodynia in neuropathic pain, while the TSPO inhibitor PK 11195 exacerbated it. The analgesic effects of AC-5216 and neurosteroids were significantly attenuated by the GABA A R antagonist bicuculline. These results suggested that elevated neurosteroids in the lateral thalamus play a protective role in the chronic stage of neuropathic pain.

show abstract

Section: Up-regulation Of Neurosteroids In the Lateral Thalamus Reliesupporting

confidence: 92%

Elevated Neurosteroids in the Lateral Thalamus Relieve Neuropathic Pain in Rats with Spared Nerve Injury

et al. 2016

View full text Add to dashboard Cite

show abstract

“…Indeed, male rodents are recognized as more sensitive to olfactory exposure to males, including men, causing stress and related analgesia [ 64 ]. Moreover, sexual dimorphism [ 65 ] and hormonal influence [ 66 , 67 ] have been observed in endogenous pain modulation mechanisms. Finally, women are more represented in the field of chronic pain [ 68 ]; however, many reasons have been explored to investigate this finding [ 69 ].…”

Section: Discussionmentioning

confidence: 99%

Concurrent validity of different functional and neuroproteomic pain assessment methods in the rat osteoarthritis monosodium iodoacetate (MIA) model

et al. 2016

View full text Add to dashboard Cite

BackgroundLack of validity in osteoarthritis pain models and assessment methods is suspected. Our goal was to 1) assess the repeatability and reproducibility of measurement and the influence of environment, and acclimatization, to different pain assessment outcomes in normal rats, and 2) test the concurrent validity of the most reliable methods in relation to the expression of different spinal neuropeptides in a chemical model of osteoarthritic pain.MethodsRepeatability and inter-rater reliability of reflexive nociceptive mechanical thresholds, spontaneous static weight-bearing, treadmill, rotarod, and operant place escape/avoidance paradigm (PEAP) were assessed by the intraclass correlation coefficient (ICC). The most reliable acclimatization protocol was determined by comparing coefficients of variation. In a pilot comparative study, the sensitivity and responsiveness to treatment of the most reliable methods were tested in the monosodium iodoacetate (MIA) model over 21 days. Two MIA (2 mg) groups (including one lidocaine treatment group) and one sham group (0.9 % saline) received an intra-articular (50 μL) injection.ResultsNo effect of environment (observer, inverted circadian cycle, or exercise) was observed; all tested methods except mechanical sensitivity (ICC <0.3), offered good repeatability (ICC ≥0.7). The most reliable acclimatization protocol included five assessments over two weeks. MIA-related osteoarthritic change in pain was demonstrated with static weight-bearing, punctate tactile allodynia evaluation, treadmill exercise and operant PEAP, the latter being the most responsive to analgesic intra-articular lidocaine. Substance P and calcitonin gene-related peptide were higher in MIA groups compared to naive (adjusted P (adj-P) = 0.016) or sham-treated (adj-P = 0.029) rats. Repeated post-MIA lidocaine injection resulted in 34 times lower downregulation for spinal substance P compared to MIA alone (adj-P = 0.029), with a concomitant increase of 17 % in time spent on the PEAP dark side (indicative of increased comfort).ConclusionThis study of normal rats and rats with pain established the most reliable and sensitive pain assessment methods and an optimized acclimatization protocol. Operant PEAP testing was more responsive to lidocaine analgesia than other tests used, while neuropeptide spinal concentration is an objective quantification method attractive to support and validate different centralized pain functional assessment methods.

show abstract

“…Progesterone is the other steroid hormone that, together with estradiol, regulates the estral cycle in rodents and the menstrual cycle in humans. There are a plethora of studies linking progesterone to anti-nociception in neuropathic pain models (Coronel et al, 2011 , 2016 ; Verdi et al, 2013 ; Jarahi et al, 2014 ; Liu et al, 2014 ). In this context, the few studies that investigated the putative effects of progesterone in the expression and functional modulation of thermoTRPs showed mainly an inhibitory role of this hormone.…”

Section: Trpv1 and Progesteronementioning

confidence: 99%

TRP Channels as Potential Targets for Sex-Related Differences in Migraine Pain

Artero-Morales

González-Rodríguez

Ferrer-Montiel

2018

Front. Mol. Biosci.

View full text Add to dashboard Cite

Chronic pain is one of the most debilitating human diseases and represents a social and economic burden for our society. Great efforts are being made to understand the molecular and cellular mechanisms underlying the pathophysiology of pain transduction. It is particularly noteworthy that some types of chronic pain, such as migraine, display a remarkable sex dimorphism, being up to three times more prevalent in women than in men. This gender prevalence in migraine appears to be related to sex differences arising from both gonadal and genetic factors. Indeed, the functionality of the somatosensory, immune, and endothelial systems seems modulated by sex hormones, as well as by X-linked genes differentially expressed during development. Here, we review the current data on the modulation of the somatosensory system functionality by gonadal hormones. Although this is still an area that requires intense investigation, there is evidence suggesting a direct regulation of nociceptor activity by sex hormones at the transcriptional, translational, and functional levels. Data are being accumulated on the effect of sex hormones on TRP channels such as TRPV1 that make pivotal contributions to nociceptor excitability and sensitization in migraine and other chronic pain syndromes. These data suggest that modulation of TRP channels' expression and/or activity by gonadal hormones provide novel pathways for drug intervention that may be useful for targeting the sex dimorphism observed in migraine.

show abstract

Early repeated administration of progesterone improves the recovery of neuropathic pain and modulates spinal 18kDa-translocator protein (TSPO) expression

Cited by 20 publications

References 43 publications

Elevated Neurosteroids in the Lateral Thalamus Relieve Neuropathic Pain in Rats with Spared Nerve Injury

Elevated Neurosteroids in the Lateral Thalamus Relieve Neuropathic Pain in Rats with Spared Nerve Injury

Concurrent validity of different functional and neuroproteomic pain assessment methods in the rat osteoarthritis monosodium iodoacetate (MIA) model

TRP Channels as Potential Targets for Sex-Related Differences in Migraine Pain

Contact Info

Product

Resources

About