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Capsaicin-induced pain and sensitisation in the postpartum period.

ABSTRACT: BACKGROUND:Recovery from Caesarean delivery in women and surgical nerve injury in animals after delivery is more rapid than expected, an effect reversed in animals by spinal injection of an oxytocin receptor antagonist. We hypothesised that endogenous modulation of acute pain is altered postpartum. METHODS:Endogenous inhibition of acute pain in a conditioned pain modulation paradigm or endogenous sensitisation by topical capsaicin was tested in women who were breastfeeding 10-14 days after Caesarean delivery and age-matched controls (n=80 total: 20 per group and 20 per test). The study was powered to detect a difference in area of hyperalgesia after capsaicin of 33%. Capsaicin-evoked pain was recorded in women, and capsaicin-evoked mechanical hypersensitivity was measured in rats 48 h after delivery and in age-matched female and male animals. RESULTS:There was no effect of the postpartum period in the endogenous sensitisation assay in women, and the conditioned pain modulation assay failed to produce analgesia in either group. Postpartum women, however, reported less intense pain than controls at the end of topical capsaicin exposure (1.3 [1.4] vs 2.0 [2.0] on 0-10 verbal scale), and acute hypersensitivity after capsaicin was less in postpartum than control rats (withdrawal threshold 25 [15] vs 3.6 [1] g). CONCLUSIONS:These results agree with a recent report that oxytocin may desensitise the transient receptor potential for vanilloid-1 channel, although other explanations, including hormone effects, are possible. These results do not, however, support the inhibition of capsaicin-evoked spinal sensitisation in the postpartum period. CLINICAL TRIAL REGISTRATION:NCT01843517.

SUBMITTER: Street LM

PROVIDER: S-EPMC6334559 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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Capsaicin-induced pain and sensitisation in the postpartum period.

Street L M LM Harris L L Curry R S RS Eisenach J C JC

British journal of anaesthesia 20181116 1

<h4>Background</h4>Recovery from Caesarean delivery in women and surgical nerve injury in animals after delivery is more rapid than expected, an effect reversed in animals by spinal injection of an oxytocin receptor antagonist. We hypothesised that endogenous modulation of acute pain is altered postpartum.<h4>Methods</h4>Endogenous inhibition of acute pain in a conditioned pain modulation paradigm or endogenous sensitisation by topical capsaicin was tested in women who were breastfeeding 10-14 d ...[more]

PMID: 30579387

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Project description:BACKGROUND:Approximately 20% of the adult population suffer from chronic pain that is not adequately treated by current therapies, highlighting a great need for improved treatment options. To develop effective analgesics, experimental human and animal models of pain are critical. Topically/intra-dermally applied capsaicin induces hyperalgesia and allodynia to thermal and tactile stimuli that mimics chronic pain and is a useful translation from preclinical research to clinical investigation. Many behavioral and self-report studies of pain have exploited the use of the capsaicin pain model, but objective biomarker correlates of the capsaicin augmented nociceptive response in nonhuman primates remains to be explored. METHODOLOGY:Here we establish an aversive capsaicin-induced fMRI model using non-noxious heat stimuli in Cynomolgus monkeys (n = 8). BOLD fMRI data were collected during thermal challenge (ON:20 s/42°C; OFF:40 s/35°C, 4-cycle) at baseline and 30 min post-capsaicin (0.1 mg, topical, forearm) application. Tail withdrawal behavioral studies were also conducted in the same animals using 42°C or 48°C water bath pre- and post- capsaicin application (0.1 mg, subcutaneous, tail). PRINCIPAL FINDINGS:Group comparisons between pre- and post-capsaicin application revealed significant BOLD signal increases in brain regions associated with the 'pain matrix', including somatosensory, frontal, and cingulate cortices, as well as the cerebellum (paired t-test, p<0.02, n = 8), while no significant change was found after the vehicle application. The tail withdrawal behavioral study demonstrated a significant main effect of temperature and a trend towards capsaicin induced reduction of latency at both temperatures. CONCLUSIONS:These findings provide insights into the specific brain regions involved with aversive, 'pain-like', responses in a nonhuman primate model. Future studies may employ both behavioral and fMRI measures as translational biomarkers to gain deeper understanding of pain processing and evaluate the preclinical efficacy of novel analgesics.

Project description:ObjectiveTo evaluate racial and ethnic differences in women's postpartum pain scores, inpatient opioid administration, and discharge opioid prescriptions.MethodsWe conducted a retrospective cohort study of all deliveries at a single high-volume tertiary care center from December 1, 2015, through November 30, 2016. Women were included if they self-identified as non-Hispanic white, non-Hispanic black, or Hispanic; were at least 18 years of age; and did not have documented allergies to nonsteroidal antiinflammatory drugs or morphine. Medical records were queried for three outcomes: 1) patient-reported postpartum pain score (on a scale of 0-10) at discharge (dichotomized less than 5 or 5 or higher), 2) inpatient opioid dosing during postpartum hospitalization (reported as morphine milligram equivalents [MMEs] per postpartum day), and 3) receipt of an opioid prescription at discharge. The associations between each of these outcomes and maternal race-ethnicity were assessed using multivariable logistic regression models with random effects to account for clustering by discharge physician. A sensitivity analysis was conducted in which women of different race and ethnicity were matched using propensity scores.ResultsA total of 9,900 postpartum women were eligible for analysis. Compared with non-Hispanic white women, Hispanic and non-Hispanic black women had significantly greater odds of reporting a pain score of 5 or higher (adjusted odds ratio [aOR] 1.61, 95% 1.26-2.06 and aOR 2.18, 95% 1.63-2.91, respectively) but received significantly fewer inpatient MMEs/d (adjusted β -5.03, 95% CI -6.91 to -3.15, and adjusted β -3.54, 95% CI -5.88 to -1.20, respectively). Additionally, Hispanic and non-Hispanic black women were significantly less likely to receive an opioid prescription at discharge (aOR 0.80, 95% CI 0.67 to -0.96 and aOR 0.78, 95% CI 0.62-0.98) compared with non-Hispanic white women. Results of the propensity score analysis largely corroborated those of the primary analysis, with the exception that the difference in inpatient MMEs/d between non-Hispanic white and non-Hispanic black women did not reach statistical significance.ConclusionHispanic and non-Hispanic black women experience disparities in pain management in the postpartum setting that cannot be explained by less perceived pain.

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Capsaicin-induced pain and sensitisation in the postpartum period.

Publications

Capsaicin-induced pain and sensitisation in the postpartum period.

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