Dissimilar interaction of opioid receptors may explain why men and women experience pain differently

Thursday 22 August 2013

Islamabad, Aug 23 (Newswire): Women and men experience pain, particularly chronic pain, very differently.

The ability of some opioids to relieve pain also differs between women and men. While it has been recognized since the mid-nineties that some narcotic analgesics are more effective in women than men, the reason for this difference was largely unknown.

Narcotic analgesics decrease pain by activating opioid receptors, which are located on nerves that transmit painful sensations. Since levels of mu, delta, and kappa opiate receptors -- the three main types of opioid receptor in the brain and spinal cord -- are not thought to differ dramatically in men and women, it was difficult to understand why the effectiveness of some painkillers is dependent on sex.

Now, research supported by the National Institute of Drug Abuse (NIDA) has revealed that the same major types of opioid receptor interact differently, depending on sex.

The spinal cord of female laboratory animals was found to contain almost five times more kappa-mu heterodimer -- a complex of mu-opioid and kappa-opioid receptor -- than the spinal cord of male animals. Furthermore, the amount of mu-kappa heterodimer in the spinal cord of the females was about four times higher when their levels of estrogen and progesterone were at their peak. Subsequently, researchers found that both estrogen and progesterone are critical for the formation of mu-kappa opioid receptor heterodimers.

The discovery of a mu-kappa opioid receptor complex that is more prevalent in the spinal cord of females than males and that is synchronized with the ebb and flow of ovarian hormones could explain why drugs used to treat pain, such as pentazocine, nalbuphine, and butorphanol -- which primarily act on mu-opioid and kappa-opioid receptors -- are more effective in women than men. The activation of the kappa-opioid receptor within the kappa-mu-opioid receptor complex could provide a mechanism for recruiting the pain-relieving functions of spinal kappa-opioid receptors without also activating their pain-promoting functions.

The research by Drs. Gintzler, Liu, and Chakrabarti, which was recently published in the Proceedings of the National Academy of Sciences and the Journal of Neuroscience, suggests that kappa-mu opioid receptor heterodimers could function as a molecular switch that shifts the action of kappa-opioid receptors and endogenous chemicals that act on them from pain-promoting to pain-alleviating. Kappa-mu opioid receptor heterodimers could serve as a novel molecular target for pain management in women.

Dr. Gintzler's research suggests that physicians should take the stage of the menstrual cycle into account before deciding which drugs to prescribe to treat pain in women. While some drugs might be very effective in treating pain at times when estrogen and progesterone levels are high, they could heighten pain when levels are low. "This consideration could become even more critical in managing pain in postmenopausal and elderly women," said Dr. Gintzler. "Further research is needed to flesh out these possibilities."

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Researchers alarmed at rise in hookah use among California youth

Islamabad, Aug 23 (Newswire): Hookah use among California youth ages 18 to 24 is rising rapidly according to a study conducted by researchers at University of California, San Diego School of Medicine.

The study appears in the "First Look" online version of American Journal of Public Health.

Researchers say the increased popularity of the hookah -- a water pipe used for smoking tobacco -- may be caused by the social nature of the behavior coupled with the misguided belief that it is less harmful than cigarettes.

"This rise is particularly alarming because it's happening in California, a state that leads the nation in tobacco control," said Wael Al-Delaimy, MD, PhD, associate professor and chief of the Division of Global Health in the UCSD Department of Family and Preventive Medicine. "While cigarette smoking has decreased nationwide and in California, reports of ever using hookah have increased, especially among adolescent and young adults."

Most users report smoking hookah with many friends, according to Al-Delaimy. "Though public indoor cigarette smoking is banned throughout California, hookah use is permitted in designated lounges. This may create the impression that hookah is a safer alternative to cigarettes, which is simply not true."

The UCSD research team used data from the state-wide California Tobacco Surveys that are led and directed by Al-Delaimy. This data on hookah is the largest representative sample on hookah use collected at different points in time from the same source population.

Study results showed that from 2005 to 2008, hookah use among all adults increased by more than 40 percent; and by 2008, hookah use in California was much higher among young adults -- 24.5 percent among men, 10 percent among women -- than it was among all adults -- 11.2 percent among men, 2.8 percent among women.

Al-Delaimy's team also found that hookah smoking among men and women was more common among non-Hispanic Whites, with at least some college education. Unlike cigarette smoking -- where those with higher education smoke less -- hookah use is higher among those who are more educated.

"More specific studies are warranted but we urge policymakers to consider laws that would ban hookah lounges, thus eliminating the implication that hookah smoking is safer and more socially acceptable than cigarette smoking," said Al-Delaimy.

In addition to Al-Delaimy, the research team includes Joshua Smith, PhD, MPH, UCSD Department of Family and Preventive Medicine; Tomas E. Novotny, MD, MPH, San Diego State University; Steven D. Edland, PhD, UCSD Department of Family and Preventive Medicine;

Richard Hostetter, PhD, San Diego State University; and Suzanne P. Lindsay, PhD, MSW, MPH, San Diego State University. Data collection for the California Tobacco Survey was funded through a contract with the California Department of Health Services.

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Triple therapy regime puts patients with leukemic form of cutaneous lymphoma in remission

Islamabad, Aug 23 (Newswire): A three-pronged immunotherapy approach nearly doubles five-year survival among patients with rare leukemic form of cutaneous T-cell lymphoma, reports a new study by dermatologists from the Abramson Cancer Center and Perelman School of Medicine at the University of Pennsylvania.

In a retrospective study of 98 patients with advanced Sezary Syndrome -- treated over a 25 year time span at the Hospital of the University of Pennsylvania -- patients treated with combination therapy experienced a higher overall response rate compared to previous studies (74.4 percent vs. 63 percent), and a higher complete response rate (30 percent vs. 20 percent). The 5-year overall survival rate was also higher than previously reported (55 percent vs. 30 percent). Researchers concluded that combination immunotherapy is more effective than a single treatment.

"This rare disease, if caught soon enough, may no longer be fatal, thanks to advances in treatment and our understanding of the disease," said Alain Rook, MD, professor of Dermatology and senior author of the study, which appears online in the Archives of Dermatology, a JAMA/Archives journal.

"In addition, our improved understanding of prognostic factors will help us tailor treatments for each patient, based on the aggressiveness of their disease, and better predict individual patient outcomes."

Sezary Syndrome is difficult to treat and has had a poor prognosis. In patients with Sezary Syndrome, malignant T-cells proliferate in the blood, while skin on the surface becomes inflamed, scaly and extremely itchy and doesn't respond to typical skin treatments. The lymphoma circulates in the blood, and tumors spread to the lymph nodes and internal organs. Typically, in the past, as few as 30 percent of patients survived 5 years with Sezary Syndrome; on average, patients survived 40 months after diagnosis.

In the Penn study, patients with advanced Sezary Syndrome received multimodality immunotherapy composed of extracorporeal photopheresis (ECP) and one or more systemic immunostimulatory agents such as interferon alpha, interferon gamma and/or retinoids.

Patients treated at earlier stages of the disease fared better. A complete response, defined as complete clearance of skin, blood and node involvement for at least 4 weeks, was seen in 30 percent of patients (n= 29).

Partial response was found in 45 percent of patients (44). The 5-year survival rate for all groups was 55 percent, and was highest in subsets of patients with stage IIIB disease (80 percent), IVA1 (80 percent), IVA2 (76 percent). Overall median survival time was 65 months; for patients with stage IVA1, median survival was 12 years; stage IVA2, 7 years. For patients with stage IIIB, median survival could not yet be calculated because many patients are still living.

Researchers also identified biological factors to help predict how each patient would respond to treatment. They confirmed that patients with a higher circulating tumor burden had a poor response to treatment. Patients with a higher number of antigen-presenting cells had better outcomes, potentially because antigen-presenting cells process the tumor cells killed by ECP treatment.

Based on this research, the efficacy of combination immunotherapy and increased understanding of the disease response to treatments will significantly extend the lives of patients with Sezary Syndrome.

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