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Louis, St. HO-1 degrades reactive, cell-free heme into antioxidants like biliverdin and carbon monoxide CO. We found that high heme or low HO-1 caused hyperalgesia in animals, likely through multiple mechanisms.

CORM-A1 also attenuated mechanical and thermal cold allodynia in hemolytic mice. Together, the data suggest that mast cell activation secondary to high heme or low HO-1 seen in cells and animals correlates with elevated plasma levels of heme, histamine, and bradykinin in PWH with CWP. Chronic widespread pain CWP is a debilitating condition that affects many individuals but has an increased prevalence in people diagnosed with human immunodeficiency virus-1 HIV-1 [ 1 , 2 ].

There is a heavy reliance on opioids to alleviate pain among PWH [ 7 ]. A history of opioid substance abuse in PWH requires higher doses for pain management and consequently increases the risk of opioid dependence. Therefore, the development of novel therapeutics is necessary to decrease opioid-related substance abuse in this population. Mast cells play an important role in stress-mediated responses and are known to be activated during neuroinflammation [ 8 , 9 , 10 ].