Effects of tonic muscle pain on fusimotor control of human muscle spindles during isometric ankle dorsiflexion.

Studies on anesthetized animals have revealed that nociceptors can excite fusimotor neurons and thereby change the sensitivity of muscle spindles to stretch; such nociceptive reflexes have been suggested to underlie the mechanisms that lead to chronic musculoskeletal pain syndromes. However, the validity of the "vicious cycle" hypothesis in humans has yielded results contrasting with those found in animals. Given that spindle firing rates are much lower in humans than in animals, it is possible that some of the discrepancies between human experimental data and those obtained in animals could be explained by differences in background fusimotor drive when the leg muscles are relaxed. We examined the effects of tonic muscle pain during voluntary contractions of the ankle dorsiflexors. Unitary recordings were obtained from 10 fusimotor-driven muscle spindle afferents (6 primary, 4 secondary) supplying the ankle dorsiflexors via a microelectrode inserted percutaneously into the common peroneal nerve. A series of 1-min weak contractions was performed at rest and during 1 h of muscle pain induced by intramuscular infusion of 5% hypertonic saline into the tibialis anterior muscle. We did not observe any statistically significant increases in muscle spindle firing rates of six afferents followed during tonic muscle pain, although discharge variability increased slightly. Furthermore, a participant's capacity to maintain a constant level of force, while relying on proprioceptive feedback in the absence of visual feedback, was not compromised during pain. We conclude that nociceptive inputs from contracting muscle do not excite fusimotor neurons during voluntary isometric contractions in humans. NEW & NOTEWORTHY Data obtained in the cat have shown that muscle pain causes a marked increase in the firing of muscle spindles, attributed to a nociceptor-driven fusimotor reflex. However, our studies of muscle spindles in relaxed leg muscles failed to find any effect on spindle discharge. Here we showed that experimental muscle pain failed to increase the firing of muscle spindle afferents during weak voluntary contractions, when fusimotor drive sufficient to increase their firing is present.

Autonomic dysreflexia: Somatosympathetic and viscerosympathetic vasoconstrictor responses to innocuous and noxious sensory stimulation below lesion in human spinal cord injury.

Autonomic dysreflexia is a dangerous elevation in blood pressure in people with spinal cord injury (SCI), produced by a spinally-mediated reflex activation of sympathetic vasoconstrictor neurones supplying skeletal muscle and the gut. Current dogma states that, apart from visceral inputs - such as those originating from a distended bladder or impacted colon - autonomic dysreflexia is triggered by noxious inputs below the lesion. However, while selective stimulation of small-diameter afferents in muscle or skin evokes a sustained increase in muscle sympathetic nerve activity and blood pressure, and a transient increase in skin sympathetic nerve activity and decrease in skin blood flow in able-bodied subjects, such noxious inputs have no effects on blood pressure and skin blood flow in SCI individuals. Conversely, weak electrical stimulation over the abdominal wall, which in able-bodied subjects is not painful and activates large-diameter cutaneous afferents, causes a marked increase in blood pressure in SCI but not in able-bodied subjects. Moreover, vibration of the penis in spinal-injured men, which is not noxious, caused marked vasoconstriction and increases in blood pressure, similar to those produced by non-noxious distension of the bladder during urodynamics procedures. This suggests that activation of large-diameter somatic afferents, not small-diameter afferents, triggers the increases in vasoconstrictor drive that lead to autonomic dysreflexia, arguing against current dogma on the importance of noxious inputs in triggering autonomic dysreflexia.

Sympathetic Responses to Noxious Stimulation of Muscle and Skin.

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.

Viscerosympathetic reflexes in human spinal cord injury: relationships between detrusor pressure, blood pressure and skin blood flow during bladder distension.

Autonomic dysreflexia, a dangerous and sustained increase in blood pressure brought about by widespread, reflexly generated vasoconstriction, can be induced by visceral or somatic sensory inputs originating below the lesion following spinal cord injury (SCI). We assessed whether cutaneous vasoconstriction below the lesion could serve as a proxy marker of incipient autonomic dysreflexia during bladder distension. Skin blood flow (pulse plethysmography), sweat release, blood pressure, heart rate, bladder and rectal pressures were recorded during routine cystometry (urodynamics) in 16 patients with SCI. Eight urological patients without SCI served as control subjects. In all SCI patients, who had sustained injuries 2 months to 44 years previously at levels C3-T3, bladder filling (mean ± SD, 339 ± 132 ml) induced increases in detrusor (bladder-rectal) pressure (52 ± 25 cmH(2)O) and cutaneous vasoconstriction in the fingers, but no consistent increases in sweat release. This occurred irrespective of whether the spinal lesions were complete [American Spinal Injury Association (ASIA) grade A, n = 6] or incomplete (ASIA B-D; n = 10). Group mean blood pressure for the SCI patients increased by 17 ± 15 mmHg, but in four patients the pressure decreased or did not change. Despite similar bladder volumes (423 ± 126 ml) in the control patients, the increases in detrusor pressure (14 ± 8 cmH(2)O) and blood pressure (9 ± 12 mmHg) were significantly smaller than in the SCI patients; moreover, there were no consistent changes in skin blood flow in the control subjects. In all SCI patients, changes in finger pulse amplitudes were inversely correlated to changes in detrusor pressure (mean r = -0.62 ± 0.17). Changes in finger pulse amplitudes correlated inversely to changes in blood pressure in nine of 15 patients. It is concluded that cystometry in SCI patients is associated with detrusor and cardiovascular reflex effects that are exaggerated compared with those in intact subjects and that measurement of skin blood flow from the fingers in patients with a high spinal lesion provides a supplementary, clinically useful, non-invasive and continuous marker of spinally mediated viscerosympathetic reflex activity below the lesion in such patients.

Reduced cardiac vagal modulation impacts on cognitive performance in chronic fatigue syndrome.

BACKGROUND: Cognitive difficulties and autonomic dysfunction have been reported separately in patients with chronic fatigue syndrome (CFS). A role for heart rate variability (HRV) in cognitive flexibility has been demonstrated in healthy individuals, but this relationship has not as yet been examined in CFS. The objective of this study was to examine the relationship between HRV and cognitive performance in patients with CFS. METHODS: Participants were 30 patients with CFS and 40 healthy controls; the groups were matched for age, sex, education, body mass index, and hours of moderate exercise/week. Questionnaires were used to obtain relevant medical and demographic information, and assess current symptoms and functional impairment. Electrocardiograms, perceived fatigue/effort and performance data were recorded during cognitive tasks. Between-group differences in autonomic reactivity and associations with cognitive performance were analysed. RESULTS: Patients with CFS showed no deficits in performance accuracy, but were significantly slower than healthy controls. CFS was further characterized by low and unresponsive HRV; greater heart rate (HR) reactivity and prolonged HR-recovery after cognitive challenge. Fatigue levels, perceived effort and distress did not affect cognitive performance. HRV was consistently associated with performance indices and significantly predicted variance in cognitive outcomes. CONCLUSIONS: These findings reveal for the first time an association between reduced cardiac vagal tone and cognitive impairment in CFS and confirm previous reports of diminished vagal activity.

Somatosympathetic Vasoconstrictor Reflexes in Human Spinal Cord Injury: Responses to Innocuous and Noxious Sensory Stimulation below Lesion.

It is known that the sudden increases in blood pressure associated with autonomic dysreflexia in people with spinal cord injury (SCI) are due to a spinally mediated reflex activation of sympathetic vasoconstrictor neurons supplying skeletal muscle and the gut. Apart from visceral inputs, such as those originating from a distended bladder, there is a prevailing opinion that autonomic dysreflexia can be triggered by noxious stimulation below the lesion. However, do noxious inputs really cause an increase in blood pressure in SCI? Using microelectrodes inserted into a peripheral nerve to record sympathetic nerve activity we had previously shown that selective stimulation of small-diameter afferents in muscle or skin, induced by bolus injection of hypertonic saline into the tibialis anterior muscle or the overlying skin, evokes a sustained increase in muscle sympathetic nerve activity and blood pressure and a transient increase in skin sympathetic nerve activity and decrease in skin blood flow in able-bodied subjects. We postulated that these sympathetic responses would be exaggerated in SCI, with a purely noxious stimulus causing long-lasting increases in blood pressure and long-lasting decreases in skin blood flow. Surprisingly, though, we found that intramuscular or subcutaneous injection of hypertonic saline into the leg caused negligible changes in these parameters. Conversely, weak electrical stimulation over the abdominal wall, which in able-bodied subjects is not painful and activates large-diameter cutaneous afferents, caused a marked increase in blood pressure in SCI but not in able-bodied subjects. This suggests that it is activation of large-diameter somatic afferents, not small-diameter afferents, that triggers increases in sympathetic outflow in SCI. Whether the responses to activation of large-diameter afferents reflect plastic changes in the spinal cord in SCI is unknown.

Autonomic hyper-vigilance in post-infective fatigue syndrome.

This study examined whether post-infective fatigue syndrome (PIFS) is associated with a disturbance in bidirectional autonomic signalling resulting in heightened perception of symptoms and sensations from the body in conjunction with autonomic hyper-reactivity to perceived challenges. We studied 23 patients with PIFS and 25 healthy matched control subjects. A heartbeat discrimination task and a pressure pain threshold test were used to assess interoceptive sensitivity. Cardiac response was assessed over a 4-min Stroop task. PIFS was associated with higher accuracy in heartbeat discrimination and a lower pressure pain threshold. Increased interoceptive sensitivity correlated strongly with current symptoms and potentiated differences in the cardiac response to the Stroop task, which in PIFS was characterized by insensitivity to task difficulty and lack of habituation. Our results provide the first evidence of heightened interoceptive sensitivity in PIFS. Together with the distinct pattern in cardiac responsivity these findings present a picture of physiological hyper-vigilance and response inflexibility.

The effects of experimental muscle and skin pain on the static stretch sensitivity of human muscle spindles in relaxed leg muscles.

Animal studies have shown that noxious inputs onto gamma-motoneurons can cause an increase in the activity of muscle spindles, and it has been proposed that this causes a fusimotor-driven increase in muscle stiffness that is believed to underlie many chronic pain syndromes. To test whether experimental pain also acts on the fusimotor system in humans, unitary recordings were made from 19 spindle afferents (12 Ia, 7 II) located in the ankle and toe extensors or peronei muscles of awake human subjects. Muscle pain was induced by bolus intramuscular injection of 0.5 ml 5% hypertonic saline into tibialis anterior (TA); skin pain was induced by 0.2 ml injection into the overlying skin. Changes in fusimotor drive to the muscle spindles were inferred from changes in the mean discharge frequency and discharge variability of spindle endings in relaxed muscle. During muscle pain no afferents increased their discharge activity: seven afferents (5 Ia, 2 II) showed a decrease and six (4 Ia, 2 II) afferents were not affected. During skin pain of 13 afferents discharge rate increased in one (Ia) and decreased in two (1 Ia, 1 II). On average, the overall discharge rate decreased during muscle pain by 6.1% (P < 0.05; Wilcoxon), but remained essentially the same during skin pain. There was no detectable correlation between subjective pain level and the small change in discharge rate of muscle spindles. Irrespective of the type of pain, discharge variability parameters were not influenced (P > 0.05; Wilcoxon). We conclude that, contrary to the 'vicious cycle' hypothesis, acute activation of muscle or skin nociceptors does not cause a reflex increase in fusimotor drive in humans. Rather, our results are more aligned with the pain adaptation model, based on clinical studies predicting pain-induced reductions of agonist muscle activity.