Peripheral DAMGO Decreases Group III and IV Afferents' Responses to Contraction in Rats Whose Femoral Arteries are Occluded
Authors: Harms Jonathan E. , Stone Audrey J. , Kaufman Marc P. 
Published: June 2021

Peripheral artery disease (PAD) is characterized by restricted blood flow to the legs. Patients with PAD show an exaggerated pressor response to mild exercise, an effect attributable to the exercise pressor reflex, whose afferent arm is comprised of the thinly myelinated Group III and unmyelinated Group IV afferents. We simulated the blood flow patterns to muscle in PAD by ligating the femoral artery of rats 72 hours prior to an experiment. Previously, we found that DAMGO, a mu‐opioid agonist injected into the femoral artery, attenuated the exaggerated exercise pressor reflex in rats with ligated femoral arteries. To follow on these findings, we recorded the responses of Group III and IV afferents to thirty seconds of static contraction before and after injecting DAMGO (1 μg) into the superficial epigastric artery in rats with patent femoral arteries and in rats with ligated femoral arteries.

In rats with patent femoral arteries, contraction increased afferent discharge in both Group III afferents (0.5 ± 0.2 to 2.0 ± 0.3 impulses/s, n=9, p<0.001) and Group IV afferents (0.4 ± 0.1 to 1.0 ± 0.2 imp/s, n=8, p<0.001). DAMGO did not change the responses to contraction of either Group III (0.5 ± 0.2 to 1.6 ± 0.4 imp/s; p=0.83) or Group IV (0.3 ± 0.1 to 0.7 ± 0.2 imp/s; p=0.34) afferents. In contrast, in rats with “ligated” femoral arteries, DAMGO injection (1 μg) significantly decreased the responses to contraction of both Group III afferents (n=9, p<0.01) and Group IV afferents (n=9; p<0.01).

In addition to contraction, we tested the effect of DAMGO on afferents' response to injecting the TRPV1 receptor agonist, capsaicin (0.2 μg), into the superficial epigastric artery. In rats with patent femoral arteries, approximately half (7/13) of Group III afferents responded to capsaicin (0.4 ± 0.2 to 2.4 ± 0.6 imp/s, p<0.001). DAMGO seemed to slightly, though not significantly, reduce the responses of these seven Group III afferents to capsaicin injection (p=0.27). Likewise, most (9/10) of the Group IV afferents tested responded to capsaicin (0.3 ± 0.9 to 2.1 ± 0.4 imp/s, p<0.001). DAMGO seemed to reduce the responses of these nine Group IV afferents, but the effect was not statistically significant (p=0.09).

DAMGO had no significant effect on the responses of Group III and IV afferents to capsaicin whose impulse activity was recorded from “ligated” rats. Only half (6/12) of the Group III afferents responded to capsaicin (0.5 ± 0.1 to 2.4 ± 0.4 imp/s, p<0.01); DAMGO reduced the response of these six afferents slightly, but not significantly (p=0.11). Again, most (9/11) Group IV afferents from “ligated” rats responded to capsaicin (0.4 ± 0.1 to 1.9 ± 0.3 imp/s, p<0.001), but DAMGO injection had no effect on the responses of these nine afferents (p=0.94).

These findings are in agreement with our previous studies which showed that peripheral DAMGO injection attenuated the exercise pressor reflex in rats with ligated femoral arteries. In contrast, DAMGO injection had only modest effect on the exercise pressor reflex in rats with patent femoral arteries. Together, these studies suggest potential therapeutic value in using opioids peripherally to treat patients with PAD, with less risk of adverse side effects and dependence.

Support or Funding Information

Funded by NIH grants R01 AR059397 and P01 HL134609‐01

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.