Can anesthetic techniques or drugs affect cancer recurrence in patients undergoing cancer surgery?

Despite the development of effective chemotherapy and radiotherapy, surgery remains the mainstay treatment of many cancers, requiring anesthesia. Almost all cancer deaths after primary surgery are attributable to recurrence or metastases. Recently it has been hypothesized that the perioperative anesthetic management of cancer patients could potentially affect the risk of recurrence and metastases, which implies a key role for anesthesiologists in choosing anesthetic agents and techniques that optimize the balance between the metastatic potential of the tumor versus its elimination by antimetastatic immune defenses.

Human peripheral blood mononuclear cells produce pre-pro-nociceptin/orphanin FQ mRNA.

Background: Peripheral blood mononuclear cells (PBMC) transcribe mRNA for the nonclassical opioid nociceptin/orphanin FQ (N/OFQ) receptor (NOP). We probed for the N/OFQ precursor, pre-pro-N/OFQ (ppN/OFQ).

Methods: Using PBMC from 10 healthy volunteers we probed for ppN/OFQ using polymerase chain reaction (PCR) based experimental paradigms.

Human peripheral blood mononuclear cells express nociceptin/orphanin FQ, but not mu, delta, or kappa opioid receptors.

Background: Expression of opioid receptors on peripheral blood mononuclear cells (PBMC) is controversial. These receptors are currently classified as classical (MOP/mu/mu, DOP/delta/delta and KOP/kappa/kappa) and nonclassical NOP (nociceptin/orphanin FQ; N/OFQ).

Methods: In this volunteer study we probed for the expression of both classical and nonclassical opioid receptors using 1) radioligand binding, 2) specific antibody binding, and 3) polymerase chain reaction-based experimental paradigms.

Clinical characteristics and pain management among patients with painful peripheral neuropathic disorders in general practice settings.

Alleviating chronic pain is a global healthcare priority. Understanding the medical profile and current treatment patterns in patients with painful neuropathic disorders (PNDs) is crucial to the development of effective pain management strategies. Thus, our objective was to describe the demographic and clinical characteristics of persons with PNDs and their use of pain medications.

Cell and tissue responses of a range of Urotensin II analogs at cloned and native urotensin II receptors. Evidence for coupling promiscuity.

Urotensin II (U-II) is the peptide ligand for the G-protein-coupled U-II receptor (UT). U-II has been dubbed "the most potent vasoconstrictor identified to date". However, in vivo studies with this system are hampered by the paucity of available ligands.

The burden of neuropathic pain: results from a cross-sectional survey.

Background: There are few published data on the treatment patterns and burden of neuropathic pain. We have investigated this in a large, observational, cross-sectional survey.

Methods: We surveyed 602 patients with neuropathic pain recruited from general practitioners in six European countries.

In vitro and in vivo pharmacological characterization of the novel UT receptor ligand [Pen5,DTrp7,Dab8]urotensin II(4-11) (UFP-803).

The novel urotensin-II (U-II) receptor (UT) ligand, [Pen(5),DTrp(7),Dab(8)]U-II(4-11) (UFP-803), was pharmacologically evaluated and compared with urantide in in vitro and in vivo assays. In the rat isolated aorta, UFP-803 was inactive alone but, concentration dependently, displaced the contractile response to U-II to the right, revealing a competitive type of antagonism and a pA(2) value of 7.46.

Ethnic differences in thermal pain responses: a comparison of South Asian and White British healthy males.

The expression and report of pain is influenced by social environment and culture. Previous studies have suggested ethnically determined differences in report of pain threshold, intensity and affect. The influence of ethnic differences between White British and South Asians has remained unexplored.

N- and C-terminal modifications of nociceptin/orphanin FQ generate highly potent NOP receptor ligands.

Previous structure-activity studies on nociceptin/orphanin FQ (N/OFQ) identified [Phe(1)Psi(CH(2)NH)Gly(2)]N/OFQ(1-13)-NH(2) and [Nphe(1)]N/OFQ(1-13)-NH(2) as a N/OFQ peptide receptor (NOP) partial agonist and pure antagonist, respectively. The addition of fluorine to the Phe(4) or the insertion of a further pair of basic amino acids Arg(14)-Lys(15) generate potent agonists. On the basis of these findings, we combined in the N/OFQ-NH(2) template the chemical modifications Arg(14)-Lys(15) and (pF)Phe(4) that increase the agonist potency with those conferring partial agonist (Phe(1)Psi(CH(2)NH)Gly(2)) or pure antagonist (Nphe(1)) properties.

[(pF)Phe4,Arg14,Lys15]N/OFQ-NH2 (UFP-102), a highly potent and selective agonist of the nociceptin/orphanin FQ receptor.

A novel ligand for the nociceptin/orphanin FQ (N/OFQ) receptor (NOP), [(pF)Phe(4),Arg(14),Lys(15)]N/OFQ-NH(2) (UFP-102), has been generated by combining in the N/OFQ-NH(2) sequence two chemical modifications, [Arg(14),Lys(15)] and [(pF)Phe(4)], that have been previously demonstrated to increase potency. In vitro, UFP-102 bound with high affinity to the human NOP receptor, showed at least 200-fold selectivity over classical opioid receptors, and mimicked N/OFQ effects in CHO(hNOP) cells, isolated tissues from various species, and mouse cortical synaptosomes releasing 5-hydroxytryptamine. UFP-102 showed similar maximal effects but higher potency (2- to 48-fold) relative to N/OFQ.

Urantide mimics urotensin-II induced calcium release in cells expressing recombinant UT receptors.

Urotensin-II is the natural ligand of the UT receptor. This novel system is involved in the regulation of cardiovascular functions. Recently, a urotensin-II analog ([Pen5,DTrp7,Orn8]urotensin-II(4-11)) named urantide, has been proposed as a selective and potent UT receptor antagonist.

Lack of analgesic efficacy of oral delta-9-tetrahydrocannabinol in postoperative pain.

We have evaluated the efficacy of delta-9-tetrahydrocannabinol (delta-9-THC), the main psychoactive constituent of cannabis, in postoperative pain. In a randomized double-blind, placebo-controlled, single-dose trial, we investigated 40 women undergoing elective abdominal hysterectomy. Randomization took place when postoperative patient-controlled analgesia was discontinued on the second postoperative day.

The effect of guanethidine and local anesthetics on the electrically stimulated mouse vas deferens.

Unlabelled: Complex regional pain syndrome is often treated with the sympatholytic guanethidine and a local anesthetic in a Bier's block. The efficacy of this treatment has been questioned. Because local anesthetics inhibit the norepinephrine uptake transporter, we hypothesized that this variable efficacy results from the local inhibiting the uptake of guanethidine.

Effects of [(pF)Phe(4)]nociceptin/orphanin FQ-(1-13)NH(2) on GTPgamma(35)S binding and cAMP formation in Chinese hamster ovary cells expressing the human nociceptin/orphanin FQ receptor.

Nociceptin/orphanin FQ (N/OFQ) is the endogenous ligand for the N/OFQ receptor (NOP). In this study using Chinese hamster ovary (CHO) cells expressing the human NOP (CHO(hNOP)) and GTPgamma(35)S binding and cAMP inhibition assays, we have characterised a novel N/OFQ ligand, [(pF)Phe(4)]N/OFQ-(1-13)NH(2), ([(pF)Phe(4)]). [(pF)Phe(4)] was produced by insertion of a fluorine atom into the para position of the phenyl ring of Phe(4) of the truncated N/OFQ peptide N/OFQ-(1-13)NH(2).

Neuropathic pain and quality of life.

The overarching reason that pain patients seek medical attention is because their pain interferes with some or all aspects of their quality of life (QOL). Interventions are considered successful by the patient if QOL is improved. Simple pain scores, although providing important information, do not capture the patient's total pain experience, which includes the effect on QOL.