Glial and neuroimmune cell choreography in sexually dimorphic pain signaling. (June 2021)

• Record Type: Journal Article
• Authors: Midavaine, Élora; Côté, Jérôme; Marchand, Serge; Sarret, Philippe
• Is Part Of: Neuroscience and biobehavioral reviews. Volume 125(2021)
• Page Start: 168
• Page End: 192
• Publication Date: 2021-06
• Subjects: Sexual dimorphism -- Sex difference -- Pain -- Microglia -- T cell -- Neuropathic pain -- Inflammatory pain -- Bone cancer pain -- Morphine; Psychophysiology -- Periodicals; Human behavior -- Periodicals; Animal behavior -- Periodicals; Neurology -- Periodicals; Behavior -- Periodicals; Ethology -- Periodicals; Neurology -- Periodicals; Psychophysiologie -- Périodiques; Comportement humain -- Périodiques; Animaux -- Mœurs et comportement -- Périodiques; Neurologie -- Périodiques; Animal behavior; Human behavior; Neurology; Psychophysiology; Periodicals; Electronic journals; 573.8
• DOI: 10.1016/j.neubiorev.2021.01.023
• Languages: English
• ISSNs: 0149-7634

Abstract

Highlights: Sex differences in pain modulation and response to pharmacological treatments are strongly influenced by the immune system and hormonal status. Sex differences exist at the cellular (microglia vs T cells) and molecular levels in neuropathic and inflammatory pain conditions. Microglial signaling in chronic pain is dependent on the hormonal level, while neuronal and astroglial contributions are sex-independent. The mechanistic differences highlight the fact that analgesics are not equally effective in different types of pain and between sexes. Abstract: Chronic pain is a major global health issue that affects all populations regardless of sex, age, ethnicity/race, or country of origin, leading to persistent physical and emotional distress and to the loss of patients' autonomy and quality of life. Despite tremendous efforts in the elucidation of the mechanisms contributing to the pathogenesis of chronic pain, the identification of new potential pain targets, and the development of novel analgesics, the pharmacological treatment options available for pain management remain limited, and most novel pain medications have failed to achieve advanced clinical development, leaving many patients with unbearable and undermanaged pain. Sex-specific susceptibility to chronic pain conditions as well as sex differences in pain sensitivity, pain tolerance and analgesic efficacy are increasingly recognized in the literature and have thus prompted scientists to seek mechanistic explanations. Hence, recent findings have highlighted that the signaling mechanisms underlying pain hypersensitivity are sexually dimorphic, which sheds light on the importance of conducting preclinical and clinical pain research on both sexes and of developing sex-specific pain medications. This review thus focuses on the clinical and preclinical evidence supporting the existence of sex differences in pain neurobiology. Attention is drawn to the sexually dimorphic role of glial and immune cells, which are both recognized as key players in neuroglial maladaptive plasticity at the origin of the transition from acute pain to chronic pathological pain. Growing evidence notably attributes to microglial cells a pivotal role in the sexually dimorphic pain phenotype and in the sexually dimorphic analgesic efficacy of opioids. This review also summarizes the recent advances in understanding the pathobiology underpinning the development of pain hypersensitivity in both males and females in different types of pain conditions, with particular emphasis on the mechanistic signaling pathways driving sexually dimorphic pain responses.