Sympathetic Responses to Noxious Stimulation of Muscle and Skin

Abstract

Acute pain triggers adaptive physiological responses that serve as protective mechanisms that prevent continuing damage to tissues and cause the individual to react to remove or escape the painful stimulus. However, an extension of the pain response beyond signaling tissue damage and healing, such as in chronic pain states, serves no particular biological function; it is maladaptive. The increasing number of chronic pain sufferers is concerning, and the associated disease burden is putting healthcare systems around the world under significant pressure. The incapacitating effects of long-lasting pain are not just psychological - reflexes driven by nociceptors during the establishment of chronic pain may cause serious physiological consequences on regulation of other body systems. The sympathetic nervous system is inherently involved in a host of physiological responses evoked by noxious stimulation. Experimental animal and human models demonstrate a diverse array of heterogeneous reactions to nociception. The purpose of this review is to understand how pain affects the sympathetic nervous system by investigating the reflex cardiovascular and neural responses to acute pain and the long-lasting physiological responses to prolonged (tonic) pain. By observing the sympathetic responses to long-lasting pain, we can begin to understand the physiological consequences of long-term pain on cardiovascular regulation.

Keywords: blood pressure; cutaneous pain; muscle pain; muscle sympathetic nerve activity; nociception; skin sympathetic nerve activity.

Figure 1

Tonic muscle pain caused a dichotomy of responses in muscle sympathetic nerve activity (MSNA) (A), mean blood pressure (B), and heart rate (C). Subjects were divided into two groups: some who showed excitatory responses to muscle pain (solid black symbols) and others who showed depressed activity (open symbols) (36).

Figure 2

Representative increases in neural and effector-organ responses (A,B) and decreases (C,D) in different subjects in response to tonic muscle pain. Activity from one subject prior to tonic muscle pain (A) and 20 min post infusion (B) (ECG, electrocardiogram; BP, blood pressure; RMS, root mean square). MSNA from the common peroneal nerve shows little spontaneous activity pre-infusion (A). Note the increases in burst frequency, burst amplitude, and BP during infusion of hypertonic saline (B). By contrast, note the reduction of MSNA in another subject who showed reductions in MSNA burst frequency, burst amplitude, and BP when comparing baseline (C) to 13 min post infusion (D) [taken from Ref. (38)].

Figure 3

Changes in mean MSNA burst amplitude (A,B) and mean blood pressure (C,D) during tonic muscle pain induced by intramuscular infusion of hypertonic saline for two subjects (A,C) and (B,D) during two separate recording sessions (open and closed symbols). The subject illustrated on the left (A,C) exhibited a sustained increase in MSNA and BP during the course of infusion, while the subject illustrated on the right (B,D) showed a decrease. For both subjects, the direction of the changes was the same in both recording sessions [taken from Ref. (38)].

Figure 4

Skin sympathetic nerve activity increased around the onset of pain for both bolus injections of hypertonic saline (A) and infusions (B). Note the biphasic response seen in B in response to tonic muscle pain: a prolonged decrease in SSNA following an initial surge in activity (i), with resultant changes in skin blood flow (ii), and vascular conductance (iii). This biphasic response is presumably related to the arousal component of pain, characterized by an increase in SSNA with concomitant decreases in skin blood flow followed by decreases in SSNA and increased skin blood flow [modified from Ref. (29, 37)].