Upregulated glial cell line-derived neurotrophic factor through cyclooxygenase-2 activation in the muscle is required for mechanical hyperalgesia after exercise in rats.

Unaccustomed strenuous exercise that includes lengthening contraction (LC) often causes delayed onset muscle soreness (DOMS), characterised as muscular mechanical hyperalgesia. Previously we reported that a bradykinin-like substance released from the muscle during exercise plays a pivotal role in triggering the process of muscular mechanical hyperalgesia by upregulating nerve growth factor (NGF) in exercised muscle of rats. We show here that cyclooxygenase (COX)-2 and glial cell line-derived neurotrophic factor (GDNF) are also involved in DOMS. COX-2 inhibitors but not COX-1 inhibitors given orally before LC completely suppressed the development of DOMS, but when given 2 days after LC they failed to reverse the mechanical hyperalgesia. COX-2 mRNA and protein in exercised muscle increased six- to 13-fold in mRNA and 1.7-2-fold in protein 0-12 h after LC. COX-2 inhibitors did not suppress NGF upregulation after LC. Instead, we found GDNF mRNA was upregulated seven- to eight-fold in the exercised muscle 12 h-1 day after LC and blocked by pretreatment of COX-2 inhibitors. In situ hybridisation studies revealed that both COX-2 and GDNF mRNA signals increased at the periphery of skeletal muscle cells 12 h after LC. The accumulation of COX-2 mRNA signals was also observed in small blood vessels. Intramuscular injection of anti-GDNF antibody 2 days after LC partly reversed DOMS. Based on these findings, we conclude that GDNF upregulation through COX-2 activation is essential to mechanical hyperalgesia after exercise.

Bradykinin and nerve growth factor play pivotal roles in muscular mechanical hyperalgesia after exercise (delayed-onset muscle soreness).

Unaccustomed strenuous exercise that includes lengthening contraction (LC) often causes delayed-onset muscle soreness (DOMS), a kind of muscular mechanical hyperalgesia. The substances that induce this phenomenon are largely unknown. Peculiarly, DOMS is not perceived during and shortly after exercise, but rather is first perceived after approximately 1 d. Using B(2) bradykinin receptor antagonist HOE 140, we show here that bradykinin released during exercise plays a pivotal role in triggering the process that leads to muscular mechanical hyperalgesia. HOE 140 completely suppressed the development of muscular mechanical hyperalgesia when injected before LC, but when injected 2 d after LC failed to reverse mechanical hyperalgesia that had already developed. B(1) antagonist was ineffective, regardless of the timing of its injection. Upregulation of nerve growth factor (NGF) mRNA and protein occurred in exercised muscle over a comparable time course (12 h to 2 d after LC) for muscle mechanical hyperalgesia. Antibodies to NGF injected intramuscularly 2 d after exercise reversed muscle mechanical hyperalgesia. HOE 140 inhibited the upregulation of NGF. In contrast, shortening contraction or stretching induced neither mechanical hyperalgesia nor NGF upregulation. Bradykinin together with shortening contraction, but not bradykinin alone, reproduced lasting mechanical hyperalgesia. We also showed that rat NGF sensitized thin-fiber afferents to mechanical stimulation in the periphery after 10-20 min. Thus, NGF upregulation through activation of B(2) bradykinin receptors is essential (though not satisfactory) to mechanical hyperalgesia after exercise. The present observations explain why DOMS occurs with a delay, and why lengthening contraction but not shortening contraction induces DOMS.

Automated cardiac output measurement by transesophageal color Doppler echocardiography.

UNLABELLED: Automated cardiac output measurement (ACOM), which integrates digital color Doppler velocities in space and in time, has been validated using transthoracic echocardiography but has not been tested using transesophageal echocardiography (TEE). Therefore, we determined the feasibility of the ACOM method by TEE in 36 patients undergoing cardiovascular surgery. Regions of interest for ACOM were placed within a color sector across the main pulmonary artery (PA), the mitral annulus, and the left ventricular outflow tract. Cardiac output was determined from the PA flow, the mitral flow, and the left ventricular ejection flow at each view using the ACOM method. We compared measurements of cardiac output derived from the ACOM method with measurements simultaneously obtained by thermodilution (TD). In the mitral flow analysis, the values derived from ACOM correlated well with those from TD (R(2) = 0.85; mean difference = 0.01 +/- 0.58 L/min in the 2-chamber view; R(2) = 0.78; mean difference = -0.10 +/- 0.68 L/min in the 4-chamber view). In the PA flow analysis, the values derived from ACOM did not correlate with those from TD (R(2) = 0.30). In the left ventricular outflow tract analysis, it was very difficult to obtain the optimal view (44%) in which color Doppler flow signals adequately appeared. Using the ACOM method, we obtained good correlation and agreement for cardiac output measurements in the mitral flow analysis compared with TD. The ACOM method is a practical and rapid method to measure cardiac output by TEE analysis of mitral flow. IMPLICATIONS: Automated cardiac output measurement by transesophageal color Doppler echocardiography is a practical and rapid method to measure cardiac output. This technique is a promising new approach to echocardiographic quantification in the intraoperative setting.

Prevention of nausea and vomiting with tandospirone in adults after tympanoplasty.

UNLABELLED: We have hypothesized that the 5-hydroxytrypta-mine-1A receptor agonist tandospirone reduces postoperative nausea and vomiting (PONV). In a double-blinded, randomized design, 3 groups of 30 patients each received 1 of the following oral medications 90 min before arrival in the operating room, together with famotidine 20 mg: 1) placebo (P group), 2) tandospirone 10 mg (T10 group), or 3) tandospirone 30 mg (T30 group). Standard anesthetic regimens and techniques were applied for all patients. All episodes of PONV were recorded during the following time intervals: 0-3 h and 3-24 h after the end of general anesthesia. The incidence of a complete response, defined as no PONV and no need for other rescue antiemetics, was significantly more frequent in the T30 group than in the P group during 0-24 h (P = 0.019), especially during 3-24 h (P = 0.007) after general anesthesia. In conclusion, premedication with oral tandospirone is effective against PONV in patients undergoing tympanoplasty under general anesthesia. IMPLICATIONS: Oral tandospirone reduced the incidence of postoperative nausea and vomiting without significant adverse effects in adults undergoing tympanoplasty under general anesthesia.