Intramuscular injection of nerve growth factor (NGF) is known to induce deep-tissue mechanical hyperalgesia. In this study it was hypothesised that daily intramuscular injections of NGF produce a progressive manifestation of soreness, mechanical hyperalgesia, and temporal summation of pain. In a double-blind placebo-controlled design, 12 healthy subjects were injected on 3 days with NGF into the tibialis anterior muscle and with isotonic saline on the contralateral side. Assessments were performed before and after the injections on days 0, 1, and 2, and repeated on days 3, 6, and 10. The self-perceived muscle soreness was assessed on a Likert scale. Computer-controlled pressure algometry was used to assess the pressure pain thresholds (PPTs). Temporal summation of pain after repeated pressure stimulations was assessed by computer-controlled pressure algometry. The pain distribution following painful pressure stimulation was also recorded. Compared with baseline and isotonic saline, the NGF injections caused (P<0.05): (1) progressively increasing soreness scores from 3 hours after the first injection until day 2, after which it remained increased; (2) decreased PPTs at days 1 to 3; (3) facilitated temporal summation of pressure pain at days 1 to 10; and (4) enlarged pressure-induced pain area after the injection on day 1 to day 6. The daily injections of NGF produced a progressive manifestation of muscle soreness, mechanical hyperalgesia, temporal summation of pressure pain, and pressure-induced pain distribution. These data illustrate that the prolonged NGF application affects peripheral and central mechanisms and may reflect process in musculoskeletal pain conditions.

The objective of this study was to examine the effect of experimental knee-related pain on postural control. Twelve healthy subjects stood as quietly as possible on a movable force platform (that measured the centre of pressure and provided fast perturbations) before, during, and after experimental knee-related pain. Lower limb electromyographic (EMG) activity and joint angles were measured. Experimental pain was induced by injecting hypertonic saline into the infrapatellar fat pad (unilateral and bilateral) and isotonic saline was used for control sessions. Compared with the baseline and control sessions, unilateral and bilateral knee-related pain during quiet standing evoked (1) an increased sway displacement in the anterior-posterior direction (P < 0.05), (2) larger knee flexion (P < 0.05), and (3) larger EMG changes. Bilateral pain also induced (1) larger medial-lateral sway displacement and speed (P < 0.05) and (2) larger left hip flexion (P < 0.05). During forward perturbations, subjects leaned forward during both painful conditions when compared with baseline (P < 0.05). The additional impairment by bilateral pain suggests that the non-painful limb in unilateral pain conditions compensates for the impaired postural control. These results show that knee-related pain impairs postural stability during quiet standing, indicating the vulnerability of patients with knee pain to falls. This measure could potentially help clinicians who seek to assess how pain responses may contribute to patient's postural control and stability during quiet standing.

Stretch reflexes and motor-evoked potentials (MEPs) of a muscle are facilitated when performing intensive contraction of muscles located in a different segment (remote effect). We investigated to what extent the remote effect on MEPs in the flexor carpi radialis (FCR) in humans is modulated during sustained maximal and submaximal voluntary contractions of the ipsilateral quadriceps (remote muscle). We found that even when the force of maximal voluntary contraction (MVC) of the remote muscle declined during sustained MVC, the magnitude of the remote effect on MEPs remained constant. Maximal electrical stimulation of the remote muscle and transcranial magnetic stimulation of the corresponding motor cortex revealed that the level of voluntary activation gradually decreased during the sustained MVC. The motor response in the FCR following magnetic stimulation at the level of the foramen magnum, which preferentially elicits muscle response as a direct response of the corticospinal tract, was not modified by the remote effect during the sustained MVC. This finding suggested that the excitability of the spinal motoneuron pool remained constant. In contrast to the sustained MVC, during sustained submaximal contraction of the remote muscle, the magnitude of the remote effect on MEPs gradually increased as muscle fatigue developed. These findings suggest that the remote effect on MEPs was dependent on the level of effort driving the remote muscle, but not on the actual level of force output of the remote muscle, and that the origin of the remote effect was supraspinal, putatively upstream of the primary motor cortex.

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Although there is some evidence showing that neural coupling plays an important role in regulating coordination between the upper and lower limbs during walking, it is unclear how tightly the upper and lower limbs are linked during rhythmic movements in humans. The present study was conducted to investigate how coupling of both limbs is coordinated during independent rhythmic movement of the upper and lower limbs. Ten subjects performed simultaneous arm and leg cycling (AL cycling) at their preferred cadences without feedback for 10 s, and then were asked to voluntarily change the cadence (increase, decrease, or stop) of arm or leg cycling. Leg cycling cadence was not affected by voluntary changes in arm cadence. By contrast, arm cycling cadence was significantly altered when leg cycling cadence was changed. These results suggest the existence of a predominant lumbocervical influence of leg cycling on arm cycling during AL cycling.

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This study demonstrates that knee pain reorganizes the APAs which may destabilize the balance control. The knee pain-related reorganization of postural muscle activity during APA may be a part of the central modulation to maintain posture and protect the painful limb while preserving the reaction task movement performance.

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