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Recent animal models of experimental nerve injury have proven useful in evaluating potential sympathetic involvement in neuropathic pain syndromes. We have employed a widely adopted unilateral L 5 /L 6 spinal nerve ligation model to compare the development of mechanical allodynia with neurochemical changes both at the site of peripheral nerve injury and in the dorsal root ganglia (DRG). We have focused on the expression of neuropeptide Y (NPY), a well-studied regulatory peptide and phenotypic marker of sympathetic neurons, and functionally related Y-receptor binding sites following nerve injury. In sympathetic neurons, NPY is colocalized and coreleased with norepinephrine (NE) at peripheral sites of action. Furthermore, NPY gene expression is induced within the population of medium- and large-diameter DRG neurons of the A β -fiber class after experimental nerve injury. We therefore hypothesized that concurrent alterations in NPY and NE expression by sympathetic and sensory neurons may be a contributing factor to sympathetically-maintained neuropathic conditions. Animals with unilateral L 5 /L 6 spinal nerve ligation developed mechanical allodynia of the hind paw ipsilateral to the site of injury that persisted until sacrifice at postoperative day 10. A significant induction of preproneuropeptide Y-encoding (PPNPY) mRNA, as detected by in situ hybridization histochemistry (ISHH), occurred in populations of medium- and large-diameter DRG neurons ipsilateral to the site of injury. Immunohistochemical analysis indicated a marked decline in the number of labeled sympathetic axons positive for tyrosine hydroxylase-like and NPY-like immunoreactivities (TH-Ll and NPY-LI, respectively) proximal to the site of nerve injury and almost complete elimination of immunopositive fibers distal to the site of ligation. Whereas, the extent of colocalization of NPY-LI to TH-LI-positive sympathetic axons in unaffected L 4 or L 5 nerve segments exceeded 80%, this figure declined to approximately 50% in regenerating axons of ligated spinal nerve L 5 . The portion of NPY-LI that was not colocalized to sympathetic TH-LI-positive fibers was most likely contributed by regenerating sensory axons, consistent with marked de novo synthesis of NPY by DRG neurons. In end bulb axon terminals, i.e. morphological profiles characteristic of neuromas, NPY-LI-positive elements that were not colocalized to TH-LI-positive sympathetic elements appeared to be spatially segregated from those of sympathetic origin with colocalized TH-LI and NPY-LI. Receptor autoradiography indicated that small- and medium-diameter DRG somata of the C-fiber class normally express both Y 1 and Y 2 receptor subtypes. The pattern of the distribution of Y-receptor binding sites appeared to be relatively unaffected by spinal nerve ligation. In contrast, there was a marked increase in the density of Y 2 receptor binding sites in the proximal segment of ligated spinal nerve L 5 , consistent with previously published data indicating differential transport of the Y 2 autoregulatory receptor subtype to nerve terminals. Induction of NPY gene expression in injured DRG neurons is consistent with appearance of NPY-LI-positive end bulbs derived from regenerating sensory axons that are found in developing neuromas containing a relatively high density of transported prejunctional Y 2 receptors. Newly established functional interactions of spatially segregated sensory- and sympathetically-derived end bulbs in developing neuromas may enhance neuronal hyperexcitability engendered by aberrant electrical activity at the site of injury. Injury-related alterations in the regulatory activities of NPY released within the DRG at somally-distributed Y-receptors may also contribute to the development and/or persistence of symptoms characteristic of sympathetically-maintained pain. Finally, at later times NPY-mediated modulation of NE release from invading sympathetic axon terminals within the DRG may affect the extent of α 2 receptor-mediated neuronal hyperexcitability associated with neuropathic pain.

Background: Anesthetic and fluid management during cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) may influence 30-day postoperative outcomes. We investigated intraoperative management differences and their relation to outcomes in all consecutive patients undergoing HIPEC and CRS following the first 2 years after initiation of this surgical oncology program in a single center. Methods: Following IRB approval we retrospectively recorded demographics, intraoperative anesthetic and fluid management and 30-day postoperative cardiopulmonary, renal, infectious, neurologic, and surgical complications, mortality and length-of-stay in patients undergoing CRS and HIPEC. The Chi-square, Fisher’s exact and Wilcoxon two-sample tests were used for statistics. A p < 0.05 was significant. Results: We identified 34 patients with a mean age of 53.9 ± 11.5 years. Postoperative complications occurred in 14 patients (41%), twelve of whom (35%) had pulmonary adverse events. Patients with complications were significantly older (p=0.04) and were significantly longer hospitalized (p=0.00). Neither primary malignancy type nor intraoperative fluid replacement differed between groups. Patients with complications had mild preoperative anemia (p=0.052).

Mesenteric traction during aortic surgery produces facial flushing, reduced mean arterial pressure (MAP), and systemic vascular resistance (SVR) with increased heart rate (HR) and cardiac index (CI). Elevated 6-keto-prostaglandin-F1 alpha (6-keto-PGF1 alpha) suggests prostacyclin is the mediator. To test this hypothesis, the cyclooxygenase inhibitor, ibuprofen (n = 14), or placebo (n = 13) was administered to patients electively scheduled for aortic reconstruction. The hemodynamic measurements and plasma concentrations of prostanoids between groups were compared immediately before (0), and 5, 10, 15, 30, and 45 min following mesenteric traction. Following mesenteric traction significant differences (P less than 0.05) were observed between the ibuprofen pretreatment and placebo group over time in SVR, MAP, HR, CI, 6-keto-PGF1 alpha, and thromboxane B2 (TXB2). Significant differences between groups at individual times were found in SVR, HR, CI, 6-keto-PGF1 alpha, and TXB2. In the placebo group flushing was accompanied by reduced SVR and MAP and increased HR and CI. The greatest effect was seen at 10 min and resolved over 30 min. Plasma concentration of 6-keto-PGF1 alpha increased from 159 +/- 103 (mean +/- SEM) pg/ml to a peak value of 3,765 +/- 803 at 10 min. A late increase in TXB2 occurred with a peak value of 1,970 +/- 891 (mean +/- SEM) pg/ml at 30 min. In the ibuprofen pretreated group no significant changes occurred in hemodynamic measurements or concentrations of prostanoids. The inhibition of 6-keto-PGF1 alpha and its associated hemodynamic changes in the treatment group, but not in the placebo group, confirms the hypothesis that prostacyclin is the mediator of the mesenteric traction response in abdominal aortic surgery.

UNLABELLED We performed a randomized, prospective, parallel-group, open-label, multicenter trial to compare the effects of pre- versus postoperative interscalene block using levobupivacaine on postoperative pain and analgesic requirements. One-hundred-two outpatients scheduled for elective shoulder surgery were randomized to receive 30 mL of 0.5% levobupivacaine either preoperatively (PRE group) or postoperatively (POST group). Analgesic outcome measures during the postoperative period were: (a). time to first request for analgesic medication after surgery, (b). pain intensity using the visual analog scale at rest and during arm movement, and (c). total analgesic consumption of nonsteroidal antiinflammatory drugs and opioids. The time to first analgesic request did not differ between treatment groups. However, mean maximum pain intensity scores during the day of surgery were significantly less for the PRE group than the POST group, both at rest (P = 0.001) and after movement (P = 0.004). The mean opioid administered during surgery was lower in the PRE than the POST group (P < 0.001). Levobupivacaine was well tolerated in both treatment groups, and no adverse reactions were related to this local anesthetic. In conclusion, preoperative interscalene block with levobupivacaine provided superior pain control for the first 12 h after surgery, but this benefit was not maintained during the week after discharge because the subjects assumed control of their own pain relief as outpatients. IMPLICATIONS Preoperative interscalene block with levobupivacaine provides safe and effective analgesia for same-day elective shoulder surgery, but the benefit of this one-time intervention does not persist.

The experiments described in the present study approached nerve injury from both a biochemical and anatomical perspective by monitoring changes in expression of preprotachykinin (PPT) mRNA encoding the prototypic tachykinin substance P and related peptide species in neurons of the rat dorsal root ganglia (DRG) following unilateral chronic constriction injury of the sciatic nerve. In situ hybridization histochemistry (ISHH) analyses in conjunction with computer-assisted image processing were employed to quantify levels of PPT mRNA distributed in DRG neurons. Injury-induced changes in PPT mRNA expression by affected DRG neurons included: 1. (1) at early postoperative times, generally increased levels of PPT mRNA associated with small and intermediate-size B cells exhibiting normal morphology, 2. (2) at late postoperative times, markedly decreased levels of PPT mRNA associated with degenerating B cells, and 3. (3) induction of PPT gene expression by large A cells which is highly correlated with degenerative morphological changes. The significant aspects of these changes are discussed with special emphasis on the contribution of altered transmitter expression by DRG neurons to the pathophysiology of causalgia. In particular, the induction of PPT gene expression by many of the large neurons undergoing degenerative changes may represent an important biochemical parameter which is associated with the development and persistence of experimental allodynia.

Although the retroperitoneal aortic approach (RP) is advocated to reduce myocardial ischemia and cardiac-related death, inadequate physiologic data exist to support this contention. As the aorta is exposed via the transabdominal approach (TA) we noted some patients have manifested reduced systemic vascular resistance (SVR) associated with tachycardia, reduced blood pressure, and facial flushing. To determine whether RP offered physiologic advantages over TA we compared cardiac dynamics and blood levels of 6-keto-prostaglandin F 1α (6-keto-PGF 1α ), the stable metabolite of prostacyclin, during exposure of the aorta in 52 patients (33 with TA and 19 with RP), comparable in age, cardiac history, medications, and body surface area. Serial measurements of mean arterial pressure, heart rate, wedge pressure, pulmonary artery pressure, cardiac index, and 6-keto-PGF 1α were obtained. Results revealed decreased mean arterial pressure and systemic vascular resistance, increased cardiac index and heart rate, and facial flush occurring 10 minutes after the bowel was explored in TA. This was not observed in RP. These hemodynamic alterations correlated in time and magnitude with a fourteen fold increase in 6-keto-PGF 1α . These changes in cardiac indexes can produce increased myocardial oxygen consumption with the risk for myocardial ischemia, particularly in patients with coronary artery disease. The absence of this response to bowel exploration in RP may account for some of the observed advantages in "high-risk" aortic reconstruction. (J VASC SURG 1988;7:190-8.)