The journal of pain : official journal of the American Pain Society
-
Comparative Study
DHEAS deficiency during consumption of sustained-action prescribed opioids: evidence for opioid-induced inhibition of adrenal androgen production.
Dehydroepandrosterone (DHEA)-dehydroepiandrosterone sulfate (DHEAS) deficiency often produces fatigue, depression, weakness, and sexual dysfunction, which improve during replacement therapy. DHEAS deficiency is a sensitive marker for generalized adrenal insufficiency, but it has not been related to opioid ingestion. DHEAS values were determined in 34 male and 32 female opioid-consuming outpatients aged 35-78 years, in stable health, and in 33 male and 53 female nonopioid-consuming control subjects. No subjects used anticonvulsants or corticosteriod medications, and none had malignant, collagen-vascular, or endocrine disease other than menopause or opioid-induced androgen deficiency. Adrenocorticotropic hormone (ACTH) values were measured in 94 of 152 subjects. DHEAS levels were lower in opioid consumers than in control subjects in a dose-related pattern (P < .01), were below age-specific norms in 67% of opioid consumers and 8% of controls (P < .001), and were below our laboratory's lowest detection limit (15 mug/dL) in 29% of opioid users and 1% of controls (P < .001). DHEAS values were also lower in opioid-consuming nonsmokers than in smokers (P < .05) and were unrelated to body mass index or concurrent hormonal replacement therapy. ACTH levels were normal and unrelated to opioid use. The combination of subnormal DHEAS levels in the presence of normal ACTH values in most opioid-consuming patients suggests that these low levels result from factors other than diminished adrenal ACTH stimulation. ⋯ The study documents a dose-related DHEAS deficiency in a majority of nonhospitalized adults who are chronically consuming sustained-action oral or transdermal opioids for control of nonmalignant pain. This deficiency in these patients has not previously been recognized and is probably symptomatic. Evaluation of replacement therapy should receive high priority.
-
Our goal was to assess the patient-level burden among subjects with painful diabetic peripheral neuropathy (DPN). Community-based physicians recruited patients with painful DPN (N = 255) between April and October 2003. Patients completed a survey on pain experience (Brief Pain Inventory-DPN [BPI-DPN]), health status (EuroQoL [EQ-5D]), healthcare utilization (consults, prescription [Rx], and over-the-counter [OTC] medications), and work productivity/functioning. Patients were 61 +/- 12.8 years old and had diabetes for 12 +/- 10.3 years and painful DPN for 6.4 +/- 6.4 years; 25.5 and 62.7% had other neuropathic and musculoskeletal pain conditions. Average and worst pain scores (BPI-DPN, 0-10 scales) were 5.0 +/- 2.5 and 5.6 +/- 2.8. The mean EQ-5D utility was .5 +/- .3 (range = -.594-1). A majority (87.4%) took pain medications (Rx/OTC) in the preceding week: an average of 3.8 +/- 3.9 Rx and 2.1 +/- 1.3 OTC medications. Nearly half (46.7%) received NSAIDs. Other frequently reported medications were short/long-acting opioids (43.1%), anticonvulsants (27.1%), selective serotonin reuptake inhibitors/selective norepinephrine reuptake inhibitors (18%), and tricyclic antidepressants (11.4%). During the preceding 3 months, 59.6% had >or=2 health professional consults; 59% reported decreased home productivity; 85.5% reported activity limitations; and 64.4% of patients who worked (N = 73) reported missing work/decreased work productivity due to painful DPN. Our results underscore a substantial patient-level burden among subjects with painful DPN. ⋯ Information on the patient-level burden among painful DPN sufferers in the U.S. was previously lacking. Our results suggest that this burden is significant, evidenced by moderate-to-high pain levels, polypharmacy, health resource use, and work/activity limitations. Results also suggest suboptimal pain management and low levels of satisfaction with treatments.
-
The aim of this study was to further validate our carrageenan-induced temporomandibular joint (TMJ) inflammatory hyperalgesia model in rats by showing that administration of indomethacin before the initiation of inflammation would diminish the TMJ hyperalgesia. Using this model, we investigated whether norepinephrine and local beta-adrenoceptors contribute to the development of inflammatory TMJ hyperalgesia. Carrageenan-induced TMJ hyperalgesia was assessed by measuring the behavioral nociceptive responses, such as rubbing the orofacial region and flinching the head, induced by the injection of a low dose of 5-hydroxytryptamine into the TMJ sensitized 1 h before by a TMJ injection of carrageenan. Blockade of prostaglandin synthesis by indomethacin prior to initiation of inflammation by carrageenan significantly attenuated the TMJ hyperalgesia. The guanethidine depletion of norepinephrine or the blockade of beta(2)but not the blockade of the beta(1)-adrenoceptor by the selective adrenoceptor antagonists ICI 118.55 and atenolol, respectively, significantly reduced carrageenan-induced TMJ hyperalgesia. In the present study, we further validated our carrageenan-induced TMJ hyperalgesia model to study the mechanisms involved in inflammatory TMJ hyperalgesia and to test the analgesic effect of different types of peripheral analgesics. We also demonstrated that norepinephrine released at the site of injury contributes to the development of the inflammatory TMJ hyperalgesia by the activation of beta(2)-adrenoceptors. ⋯ The findings that local sympathomimetic amines contribute to the inflammatory TMJ hyperalgesia by activating beta(2)-adrenoceptors may be relevant to clinical TMJ inflammatory pain states less sensitive to nonsteroidal anti-inflammatory drugs.
-
Although mechanical hyperalgesia associated with medical procedures is the major source of severe pain in burn-injured patients, little is known about its underlying mechanism. One reason for this has been the lack of a model for mechanical hyperalgesia at the site of injury. We have modified an established partial-thickness burn model in the rat to produce long-lasting primary mechanical hyperalgesia, which is present from the first measurement at 0.5 h, reaches a maximum at 3 days, and is still significant after 7 days. Because nerve growth factor (NGF), which is elevated in burn-injured tissue, produces mechanical hyperalgesia and activates protein kinase C (PKC)-epsilon, a key mediator in inflammatory and neuropathic pain, we used this model to evaluate the role of the NGF receptor, tyrosine-receptor kinase A (TrkA), and PKC-epsilon in burn-induced primary mechanical hyperalgesia. Intrathecal administration of antisense oligodeoxynucleotides to TrkA and PKC-epsilon, starting 3 days before inducing a burn injury, caused dose-related decrease of burn-induced primary mechanical hyperalgesia. In addition, intradermal injection of a PKC-epsilon-selective inhibitor eliminated hyperalgesia. Our model provides a method to elucidate the underlying mechanism of burn-injury pain as well as to screen for targets for novel analgesic treatments of this important clinical condition. ⋯ This manuscript presents the first model of thermal injury-induced mechanical hyperalgesia which mimics prolonged duration of clinical burn injury pain. We also perform proof of concept experiments demonstrating that our model provides a method to elucidate the mechanism of this important clinical condition.
-
Chronic pain is one of the most prevalent and costly problems in the United States today. Traditional medical treatments for it, though, have not been consistently efficacious or cost-effective. In contrast, more recent comprehensive pain programs (CPPs) have been shown to be both therapeutically efficacious and cost-effective. The present study reviews available evidence demonstrating the therapeutic efficacy and cost-effectiveness of CPPs, relative to conventional medical treatment. Searches of the chronic pain treatment literature during the past decade were conducted for this purpose, using MEDLINE and PSYCHLIT. Studies reporting treatment outcome results for patients with chronic pain were selected, and data on the major outcome variables of self-reported pain, function, healthcare utilization and cost, medication use, work factors, and insurance claims were evaluated. When available, conventional medical treatments were used as the benchmark against which CPPs were evaluated. This review clearly demonstrates that CPPs offer the most efficacious and cost-effective, evidence-based treatment for persons with chronic pain. Unfortunately, such programs are not being taken advantage of because of short-sighted cost-containment policies of third-party payers. ⋯ A comprehensive review was conducted of all studies in the scientific literature reporting treatment outcomes for patients with chronic pain. This review clearly revealed that CPPs offer the most efficacious and cost-effective treatment for persons with chronic pain, relative to a host of widely used conventional medical treatment.