Table 1.
Summary of sex differences across various neuro-, immune-, and endocrine-based targets
| Target | Context | Sex differences | References |
|---|---|---|---|
| TRPV1 | Lung infection | Both sexes used; sex differences not assessed | (151-156) |
| Allergic airway inflammation | Sex used not stated | (154) | |
| Gut infection | Not assessed; only males | (22, 157) | |
| Colitis | Not assessed; only males | (24-26) | |
| TLR4 | LPS activation | No differences | (30, 31, 158-160) |
| Inflammatory pain | Cell-type differences: immune cell driven in males but not females | (161, 162) | |
| Macrophages | Pain signaling | Larger role in males | (161, 162, 176, 177) |
| Inflammation | Proinflammatory in males; anti-inflammatory in females and modulated by E2 | (40, 49, 55, 136, 172-175) | |
| Microglia | Pain signaling | Larger role in males | (57-60, 67, 68, 178) |
| Inflammation | More proliferative and proinflammatory in males; anti-inflammatory and greater phagocytosis in females | (51, 66) | |
| T cells | Pain signaling | Inconsistent across models: no differences, male biased, and female biased | (54, 73-76) |
| Inflammation | Females have stronger responses to infection and function is modulated by E2 | (40, 43, 45, 71, 72) | |
| Testosterone | Analgesia | Similar effects in both sexes | (77-86) |
| E2 | Pain signaling | ERs are more abundant in trigeminal sensory neurons in females, and fluctuations in E2 may be responsible for migraine attacks | (36, 87-94) |
| Inflammation | Decreases in E2 following menopause, increases proinflammatory cytokines | (91, 92) | |
| Prolactin | Pain signaling | Female-biased roles, little to no effects in males | (65, 95-101) |
| AMPK | Inflammation | Activation is anti-inflammatory in male macrophages | (111, 112, 186) |
| Pain signaling | Activation promotes pain relief in male but not female mice; reduces effects of transition from acute to chronic pain | (116, 192-195) | |
| LKB1 | Pain signaling | Increased female reproductive tract innervation in endometriosis | (189) |
| Innervation | Potentially responsive to variations in sex hormones in females | (113-115) | |
| LXR | Inflammation | Not assessed; only males | (117, 123) |
| Pain signaling | Not assessed; only males | (119, 123) | |
| PPARα | Inflammation | Protective/anti-inflammatory in males | (183, 198) |
| Pain signaling | Analgesic in males or no differences | (183, 198, 202, 203) | |
| PPARγ | Inflammation | Anti-inflammatory in macrophages, promoted by E2 | (205-207) |
| Pain signaling | Analgesic in females only (PNI) or both sexes (CIPN) | (183, 201, 204) |
Abbreviations: AMPK, adenosine 5′-monophosphate–activated protein kinase; CIPN, chemotherapy-induced neuropathy; E2, estradiol; ER, estrogen receptor; LKB1, liver kinase B1; LPS, lipopolysaccharide; LXR, liver X receptor; PNI, peripheral nerve injury; PPAR, peroxisome proliferator-activated receptor; TLR4, toll-like receptor 4; TRPV1, TRP channel, vanilloid subtype.