Substance P at the nexus of mind and body in chronic inflammation and affective disorders.

Abstract

For decades, research has demonstrated that chronic diseases characterized by dysregulation of inflammation are particularly susceptible to exacerbation by stress and emotion. Likewise, rates of depression and anxiety are overrepresented in individuals suffering from chronic inflammatory disease. In recent years, substance P has been implicated in both the pathophysiology of inflammatory disease and the pathophysiology of depression and anxiety by 2 parallel fields of study. This review integrates the literature from these 2 parallel fields and examines the possibility that substance P dysregulation may be a point of convergence underlying the overlap of chronic inflammatory disease and mood and anxiety disorders. First, the involvement of substance P in peripheral inflammation and in the immune events associated with chronic inflammatory disease is discussed, with a focus on inflammatory bowel disease and asthma. Next, the function of substance P in the communication of peripheral inflammation to the brain is considered. Finally, to complete the bidirectional loop of brain-immune interactions, substance P expression in anxiety and depression as well as its potential role in the neural regulation of peripheral inflammation is reviewed.

Depression and anxiety in inflammatory bowel disease: A review of comorbidity and management

“…Alternatively, if the lag phase before IBD is diagnosed is longer than expected, 47 perhaps there are reciprocal effects of the brewing inflammatory state that initiate a mood disorder. 11 At the very least, there is evidence that depression can significantly antedate the diagnosis of IBD at a higher rate than one would expect from comparative base rates.…”

“…[8][9][10] Alternatively, there has been significant discussion about potential common pathways, particularly between depression and inflammatory conditions such as IBD, related to dysfunctioning immunoregulatory circuits. [11][12][13] Regardless, the comorbidity can complicate functioning as well as disease outcomes. 7,14,15 A great deal of disability and functional impairment that occurs in chronic health problems is associated with anxiety and depression moreso than the features of the disease.…”

Effects of Substance P in the Amygdala, Ventromedial Hypothalamus, and Periaqueductal Gray on Fear-Potentiated Startle

“…A large number of studies have implicated Substance P (SP) in fear and anxiety based on the ability of local infusion of SP into various parts of the brain to elicit defensive and anxiety-like effects and that SP antagonists can have anxiolytic effects (compared with Rosenkranz, 2007). SP appears to influence affective behaviors, at least in part, by actions within the amygdala (Boyce et al, 2001;Ebner et al, 2004;Kramer et al, 1998;Smith et al, 1999).…”

Connections of the lateral hypothalamic area juxtadorsomedial region in the male rat

“…Taking SP as an example of an LS-expressed neurotransmitter that might be involved in LHAjd neurotransmission, this neuropeptide (along with other tachykinins) is implicated in various responses to stress (Culman and Unger, 1995;Spitznagel et al, 2001;Rosenkranz, 2007), and with regard to a more specific possible role in relation to the LHAjd-LS bidirectional connections, SP is indicated to have a role in aggressive/defensive behaviors (Katsouni et al, 2009), although the specific role of SP-expressing LS neurons remains to be clarified. Nevertheless, SP within the LS is thought to have a role in behavioral inhibition (Ebner et al, 2008), and immunohistochemical studies show an extensive and robust presence of SP-containing axons, as well as the SP receptor, in the LHA (Nakaya et al, 1994).…”