stilbenes and Chronic-Pain

Palmitoylethanolamide is reported to solve pain and neuroinflammation in different models of chronic and neurodegenerative diseases. Some concerns have been illustrated for cautiously interpreting the available literature on the topic. Specifically, there is a lack of evidence about palmitoylethanolamide and female chronic pelvic pain. Concerns will be best solved by randomized trials. The present study was aimed at finding the best responders to micronized palmitoylethanolamide in female patient with chronic pelvic pain, using the existing literature at individual patient level, to help further randomized trial planning.. After a systematic research, eligible studies (the ones enrolled female patients treated for chronic pelvic pain or for dyspareunia, dysuria, dyschezia, and dysmenorrhea with or without chronic pelvic pain) were assessed at individual patient data level. Conditional probabilities were calculated to assess variables conditioning the rates of good responders (pain score points more or equal to 3 reduction), poor responders (2 pain score reduction), and nonresponders at a three-month follow-up.. Only cases treated with palmitoylethanolamide comicronized with polydatin for a short period can be assessed. Good responders are more than 50%. In chronic pelvic pain, there is a 19.0% conditional probability to find good responders among patients with pain score at enrolment of 6 to 8 and of 6.8% to find poor responders among patients with a pain score at enrolment of 6 to 8. Painful disease does not matter on responders' rates.. Best responders to comicronized palmitoylethanolamide/polydatin are patients with pain score higher than 6 at enrolment, irrespective of other variables.

Topics: Amides; Chronic Pain; Dysmenorrhea; Endometriosis; Ethanolamines; Female; Glucosides; Humans; Palmitic Acids; Pelvic Pain; Stilbenes

Aim of the study was to evaluate the effectiveness of micronized palmitoylethanolamide (PEA)-transpolydatin in the treatment of chronic pelvic pain in women affected by endometriosis.. Twenty-four patients with suspected endometriosis affected by severe pelvic pain were enrolled. All patients received two tablets a day of PEA 400 mg and 40 mg polydatin for 90 days consecutively. A Visual Analogic Scale was used for the assessment of the severity of global pain, dysmenorrhea, dyspareunia, dysuria and dischezia. A second questionnaire was submitted to patients to assess the quality of life. The compilation of a diary lead us to evaluate the monthly assumption of any painkillers. Patients were evaluated at the begin of the treatment and then monthly until the end of the study (90 days). The statistical analysis was performed by using the ANOVA for the analysis of variance.. Statistically significant results were found in relation to pelvic pain, dysmenorrhea and dyspareunia compared to the initial evaluation of patients. Results related to dysuria and dischezia were not statistically significant (P>0.05). The decrease in pelvic pain leads to an improvement of the quality of life of patients. A decreased assumption of nonsteroidal anti-inflammatory drugs (NSAIDs) was also observed.. PEA could be considered an effective supplement to conventional analgesic therapies in the management of pelvic pain related to endometriosis.

Topics: Adult; Amides; Anti-Inflammatory Agents, Non-Steroidal; Chronic Pain; Drug Combinations; Dysmenorrhea; Dyspareunia; Endocannabinoids; Endometriosis; Ethanolamines; Female; Glucosides; Humans; Middle Aged; Palmitic Acids; Particle Size; Pelvic Pain; Pilot Projects; Quality of Life; Stilbenes; Surveys and Questionnaires; Young Adult

To assess the efficacy of a micronized-palmitoylethanolamide-polydatin (m-PEA-Pol) based product on chronic pelvic pain and severity of other symptoms in interstitial cystitis/bladder pain syndrome (IC/BPS) patients refractory to conventional therapies.. A pilot, open-label bicentric study was carried out involving 32 IC/BPS patients. Chronic, oral m-PEA-Pol treatment lasted 6 months. Bladder pain was evaluated using the visual analog scale, while changes from baseline in other urinary symptoms were evaluated by means of the O'Leary-Sant Interstitial Cystitis Symptom and Problem Index and the Pelvic Pain and Urgency/Frequency (PUF) symptom scale questionnaires. The generalized linear mixed model was used to evaluate significant mean changes across time.. A significant and progressive reduction of pain intensity was observed during m-PEA-Pol treatment (. These data highlight the potential benefit of m-PEA-Pol in patients with rare pathology such as IC/BPS and confirm the good safety profile of micronized PEA-based products.

Topics: Administration, Oral; Adult; Aged; Amides; Chronic Pain; Cystitis, Interstitial; Ethanolamines; Female; Glucosides; Humans; Male; Middle Aged; Pain Measurement; Palmitic Acids; Pelvic Pain; Pilot Projects; Stilbenes; Urination

To test the adjuvant use of the combination of N-palmitoylethanolamine and transpolydatin in the medical treatment of endometriotic pain.. We enrolled 47 patients admitted to the Outpatient Endometriosis Care Unit of Ferrara University from January 2011 to December 2011. They were divided into two groups according to the endometriosis site (group A: recto-vaginal septum; group B: ovary). One tablet, containing 400 mg of micronized N-palmitoylethanolamine plus 40 mg transpolydatin, was administered twice daily on a full stomach for 90 days. Each patient was requested to grade the severity of dysmenorrhea, chronic pelvic pain, dyspareunia and dyschezia using a 0-10 cm visual analogic scale prior to beginning treatment (T0), after 30 days (T1), 60 days (T2) and 90 days (T3). The continuous and categorical variables were compared, respectively, using Student's t-test and the chi-square test. Analysis of variance for repeated measures was used to verify the reduction of endometriotic pain.. The intensity of endometriotic pain decreased significantly for both groups (p<0.0001). The efficacy of drug treatment was significant after 30 days. Pain intensity decreased equally in the two groups except for dysmenorrhea, which was reduced more rapidly in group B.. The combination of N-palmitoylethanolamine and transpolydatin reduced pain related to endometriosis irrespective of lesion site. It had a marked effect on chronic pelvic pain determined by deep endometriosis and on dysmenorrhea correlated to ovarian endometriosis.

Topics: Adult; Amides; Anti-Inflammatory Agents, Non-Steroidal; Chronic Pain; Contraceptives, Oral, Combined; Drug Combinations; Drug Therapy, Combination; Dysmenorrhea; Endocannabinoids; Endometriosis; Ethanolamines; Fascia; Female; Female Urogenital Diseases; Glucosides; Humans; Middle Aged; Ovarian Diseases; Pain Measurement; Palmitic Acids; Pelvic Pain; Prospective Studies; Stereoisomerism; Stilbenes; Young Adult

Despite advances in our understanding of basic mechanisms driving post-surgical pain, treating incision-induced pain remains a major clinical challenge. Moreover, surgery has been implicated as a major cause of chronic pain conditions. Hence, more efficacious treatments are needed to inhibit incision-induced pain and prevent the transition to chronic pain following surgery. We reasoned that activators of AMP-activated protein kinase (AMPK) may represent a novel treatment avenue for the local treatment of incision-induced pain because AMPK activators inhibit ERK and mTOR signaling, two important pathways involved in the sensitization of peripheral nociceptors.. To test this hypothesis we used a potent and efficacious activator of AMPK, resveratrol. Our results demonstrate that resveratrol profoundly inhibits ERK and mTOR signaling in sensory neurons in a time- and concentration-dependent fashion and that these effects are mediated by AMPK activation and independent of sirtuin activity. Interleukin-6 (IL-6) is thought to play an important role in incision-induced pain and resveratrol potently inhibited IL-6-mediated signaling to ERK in sensory neurons and blocked IL-6-mediated allodynia in vivo through a local mechanism of action. Using a model of incision-induced allodynia in mice, we further demonstrate that local injection of resveratrol around the surgical wound strongly attenuates incision-induced allodynia. Intraplantar IL-6 injection and plantar incision induces persistent nociceptive sensitization to PGE2 injection into the affected paw after the resolution of allodynia to the initial stimulus. We further show that resveratrol treatment at the time of IL-6 injection or plantar incision completely blocks the development of persistent nociceptive sensitization consistent with the blockade of a transition to a chronic pain state by resveratrol treatment.. These results highlight the importance of signaling to translation control in peripheral sensitization of nociceptors and provide further evidence for activation of AMPK as a novel treatment avenue for acute and chronic pain states.

Topics: Acute Pain; AMP-Activated Protein Kinases; Animals; Chronic Pain; Disease Models, Animal; Dose-Response Relationship, Drug; Eukaryotic Initiation Factor-4F; Extracellular Signal-Regulated MAP Kinases; Hyperalgesia; Interleukin-6; Male; Mice; Mice, Inbred ICR; Pain, Postoperative; Protein Biosynthesis; Resveratrol; Sensory Receptor Cells; Signal Transduction; Sirtuin 1; Stilbenes; Time Factors; TOR Serine-Threonine Kinases; Trigeminal Ganglion