Sex differences in complex regional pain syndrome type I (CRPS-I) in mice

Abstract

BackgroundSex differences have been increasingly highlighted in complex regional pain syndrome (CRPS) in clinical practice. In CRPS type I (CRPS-I), although inflammation and oxidative stress have been implicated in its pathogenesis, whether pain behavior and the underlying mechanism are sex-specific is unclear. In the present study, we sought to explore whether sex differences have an impact on inflammation, oxidative stress, and pain sensitivity in CRPS-I.MethodsChronic post-ischemia pain (CPIP) was established in both male and female mice as an animal model of CRPS-I. Edema and mechanical allodynia of bilateral hind paws were assessed after reperfusion. Blood samples were analyzed for serum levels of oxidative stress markers and inflammatory cytokines.ResultsBoth male and female mice developed edema. Male mice developed CPIP at day 3 after reperfusion; female mice developed CPIP at day 2 after reperfusion. Female mice displayed significantly earlier and higher mechanical allodynia in the ischemic hind paw, which was associated with higher serum levels of IL-2, TNF-α, isoprostanes, 8 OhdG, and malondialdehyde at day 2 after reperfusion. Moreover, female mice showed significantly lower SOD and IL-4 compared to male mice at day 2 after reperfusion.ConclusionOur results indicate that sex differences in inflammatory and oxidative stress states may play a central role in the sex-specific nociceptive hypersensitivity in CRPS-I, and offer a new insight into pharmacology treatments to improve pain management with CRPS.

Macrophages and Schwann cell TRPA1 mediate chronic allodynia in a mouse model of complex regional pain syndrome type I

“…Although a previous study detected a moderate difference in the development of mechanical allodynia in male and female mice (Tang et al, 2017), our research group previously reported (De Prá et al, 2019) and confirm in the current study, that there is no difference in non-evoked and evoked pain responses evoked by I/R in female vs. male mice. The absence of sex-related differences in the severity of pain in CRPS-I patients (Velzen et al, 2019) is in agreement with our mouse findings.…”

TRPV1 Channel Contributes to the Behavioral Hypersensitivity in a Rat Model of Complex Regional Pain Syndrome Type 1

“…Epidemiology studies found that the incidence of CRPS-I is higher in female than male patients (Weissmann and Uziel, 2016; Kim et al, 2018). Animal studies also identified that CPIP female mice developed significantly earlier and higher mechanical allodynia in the ischemic hind paw than male mice (Tang et al, 2017). In the past decade, sex differences in pain perception have shown increasing importance in both clinical and experimental studies (Kindler et al, 2011; Boerner et al, 2017).…”

Dexmedetomidine with sufentanil in intravenous patient-controlled analgesia for relief from postoperative pain, inflammation and delirium after esophageal cancer surgery

“…In contrast, the PCA-based drug delivery system, which has its own safe individual drug titration, may also help minimize sedation [25]. The pro-inflammatory cytokines (PICs), such as IL-6 and TNF-α, and the anti-inflammatory cytokine, IL-10, are important groups of inflammatory mediators and play an essential role in pain sensitization [26][27][28]. Systemic or regional analgesic regimens could prevent both peripheral and central sensitization, thereby attenuating the postoperative amplification of pain sensation [16,29,30].…”