Endothelin-1 Exhibiting Pro-Nociceptive and Pro-Peristaltic Activities Is Increased in Peritoneal Carcinomatosis.

Background: Peritoneal carcinomatosis often results in alterations in intestinal peristalsis and recurrent abdominal pain. Pain management in these patients is often unsatisfactory. This study aimed to investigate whether endothelin-1 (EDN1) was involved in pain mediation in peritoneal carcinomatosis, and thus whether the EDN1 pathway could be a new therapeutic target for peritoneal carcinomatosis-associated pain. Methods: EDN1 plasma levels and abdominal pain severity were assessed in patients with abdominal tumors, with or without peritoneal carcinomatosis, and in healthy donors. The effects of EDN1 on the visceromotor response to colorectal distension, and on colonic contractions were then examined in mice, and the mechanism of action of EDN1 was then investigated by measuring the impact of EDN1 exposure on calcium mobilization in cultured neurons. Inhibition studies were also performed to determine if the effects of EDN1 exposure could be reversed by EDN1-specific receptor antagonists. Results: A positive correlation between EDN1 plasma levels and abdominal pain was identified in patients with peritoneal carcinomatosis. EDN1 exposure increased visceral sensitivity and the amplitude of colonic contractions in mice and induced calcium mobilization by direct binding to its receptors on sensory neurons. The effects of EDN1 were inhibited by antagonists of the EDN1 receptors. Conclusions: This preliminary study, using data from patients with peritoneal carcinomatosis combined with data from experiments performed in mice, suggests that EDN1 may play a key role mediating pain in peritoneal carcinomatosis. Our findings suggest that antagonists of the EDN1 receptors might be beneficial in the management of pain in patients with peritoneal carcinomatosis.

An Algorithm for Neuropathic Pain Management in Older People.

Neuropathic pain frequently affects older people, who generally also have several comorbidities. Elderly patients are often poly-medicated, which increases the risk of drug-drug interactions. These patients, especially those with cognitive problems, may also have restricted communication skills, making pain evaluation difficult and pain treatment challenging. Clinicians and other healthcare providers need a decisional algorithm to optimize the recognition and management of neuropathic pain. We present a decisional algorithm developed by a multidisciplinary group of experts, which focuses on pain assessment and therapeutic options for the management of neuropathic pain, particularly in the elderly. The algorithm involves four main steps: (1) detection, (2) evaluation, (3) treatment, and (4) re-evaluation. The detection of neuropathic pain is an essential step in ensuring successful management. The extent of the impact of the neuropathic pain is then assessed, generally with self-report scales, except in patients with communication difficulties who can be assessed using behavioral scales. The management of neuropathic pain frequently requires combination treatments, and recommended treatments should be prescribed with caution in these elderly patients, taking into consideration their comorbidities and potential drug-drug interactions and adverse events. This algorithm can be used in the management of neuropathic pain in the elderly to ensure timely and adequate treatment by a multidisciplinary team.

Validation of an acute pain-behavior scale for older persons with inability to communicate verbally: Algoplus.

To compensate for poor acute pain detection in elderly inpatients with inability to communicate verbally (ICV), the Doloplus Collective team devised the 5-item Algoplus behavior-assessment scale specifically aimed at quickly detecting acute pain in these individuals. Algoplus was developed in three successive phases, including expert opinions, caregivers interviews, patient video recordings and statistical procedures. Among the 1500 recorded primary pain behaviors, 48 were selected and clustered into a 5-item scale. This version was validated based on 349 old inpatients (204 with acute pain and 145 without) from different care settings and hospitals. Comparators were objective acute pain clinical situations, experts' clinical judgment on acute pain presence, and self-rating scales (Visual Analog Scale, Numeric Rating Scale and Verbal Descriptor Scale) for a communicative subsample (n=134). Algoplus showed good discriminant validity with adequate internal consistency (Kuder-Richardson-20, 0.712), excellent interrater reliability (intraclass coefficient, 0.812) and high sensitivity to change during specific pain situations and after starting pain management. Excellent correlations were observed between Algoplus and experts' clinical judgment, acute pain clinical situations or each comparator self-rating-pain score. For patients with acute pain conditions, a score ⩾2 out of 5 on the Algoplus scale was retained as the threshold for the presence of acute pain in elderly ICV inpatients, with 87% sensitivity and 80% specificity. In addition, the very brief rating time of ∼1min is particularly relevant in acute-care settings, where repetitive pain-monitoring is required.