Bradford D. Hare

The association between chronic pain and obesity

Obesity and pain present serious public health concerns in our society. Evidence strongly suggests that comorbid obesity is common in chronic pain conditions, and pain complaints are common in obese individuals. In this paper, we review the association between obesity and pain in the general population as well as chronic pain patients. We also review the relationship between obesity and pain response to noxious stimulation in animals and humans. Based upon the existing research, we present several potential mechanisms that may link the two phenomena, including mechanical/structural factors, chemical mediators, depression, sleep, and lifestyle. We discuss the clinical implications of obesity and pain, focusing on the effect of weight loss, both surgical and noninvasive, on pain. The literature suggests that the two conditions are significant comorbidities, adversely impacting each other. The nature of the relationship however is not likely to be direct, but many interacting factors appear to contribute. Weight loss for obese pain patients appears to be an important aspect of overall pain rehabilitation, although more efforts are needed to determine strategies to maintain long-term benefit.

The effects of myofascial trigger point injections are naloxone reversible

&NA; Ten patients with myofascial trigger point pain were entered into a double‐blind cross‐over study of the reversibility of myofascial trigger point injection (TPI) effects with naloxone versus placebo in order to test the hypothesis that the benefits of TPI are mediated, at least in part, through activation of an endogenous opioid system. Injection of trigger points with 0.25% bupivacaine decreased pain in all subjects and increased range of motion in subjects who, on initial assessment, demonstrated limitations of movement of the affected part(s). Allodynia and palpable bands preceding TPI when present also showed reduction after TPI. All improvements afforded by TPI were significantly reversed with intravenous naloxone (10 mg) compared to intravenous placebo. These results demonstrate a naloxone‐reversible mechanism in TPI therapy. This suggests an endogenous opioid system as a mediator for the decreased pain and improved physical findings following injection of myofascial trigger points with local anesthetic.

Iontophoretic delivery of for postoperative analgesia

Abstract Iontophoresis is a method of transdermal administration of ionized drugs in which electrically charged molecules are propelled through the skin by an external electrical field. This was a prospective, randomized, single-blind study to determine the effectiveness of iontophoretically delivered morphine HCl for the control of postoperative pain. Thirty-eight patients who underwent total knee or hip replacement completed this clinical trial. Informed consent was obtained before surgery and patients were instructed on the use of a patient-controlled analgesia (PCA) device. Postoperatively, pain in the recovery room was initially controlled with IV mependine, and thereafter with PCA therapy using meperidine, 2 mg/cc, with a dose of 10 mg IV and a lock-out period of 15 min. The dose was adjusted as necessary and the lock-out period remained the same. The number of patient requests and the dose (mg) administered was recorded hourly. On the morning following surgery, iontophoresis devices were attached for 6 hr to patients who received either morphine HCl or lactated ringers solution. During this period and for 12 hr following completion of iontophoresis, PCA analgesia remained available to patients. Venous blood samples for determination of morphine levels were obtained every 30 min during iontophoresis, then every 60 min for 2 hr following iontophoresis. Of the 38 patients, 17 received iontophoresed morphine, and 21 received iontophoresed lactated ringers. The morphine group utilized the PCA device more than the control group during the baseline period. However, following the institution of iontophoresis and continuing up to 12 hr following completion of iontophoresis, the morphine group used significantly less PCA mependine to maintain analgesia than the control group ( p = 0.001). Plasma morphine levels in patients iontophoresed with this drug revealed analgesic levels of morphine, whereas, those of control subjects were effectively zero. Adverse effects related to PCA therapy or iontophoresis were minimal. Iontophoresis can deliver morphine systemically in high enough concentrations to provide early postoperative pain relief in patients undergoing total knee or hip replacements. Further investigation into iontophoretically delivered morphine and other opioids for postoperative and long-term pain control is warranted.

Do Sleep Disorders Contribute to Pain Sensitivity

Sleep disturbance is one of the most common comorbid problems for chronic pain patients. The association between the two phenomena has long been recognized, but the nature of the relationship is not well-understood. Many agree that the relationship is likely bidirectional. In this review, we focus on one side of the relationship: whether and how disordered sleep adversely impacts pain. We discuss the available evidence from the epidemiologic, clinical, and human, as well as infrahuman laboratory studies. Generally, the literature supports the positive relationship between poor sleep and increased pain. Sleep deprivation also seems to attenuate analgesic effects of medications. Research delineating the causal or associative relationship between sleep and pain is still preliminary at this time. Continuing efforts in both experimental and clinical research are needed to develop a translationally meaningful understanding of how poor sleep impacts pain.

Depression of sympathetic preganglionic neurons by clonidine: evidence for stimulation of 5-HT receptors.

In unanesthetized spinal cats, clonidine HCl (5-50 microgram/kg, i.v.) rapidly and markedly depressed excitatory transmission through two spinal pathways to sympathetic preganglionic neurons. Depression through either pathway was dose-dependent and persisted for more than 3 hr but could be rapidly antagonized at any stage by tolazoline HCl in a dose-ratio of about 1:100. The two spinal pathways were also depressed transiently by L-dopa and for prolonged periods by 5-HTP; both precursors were shown to act by releasing 5-HT from bulbospinal 5-HT terminals and their depressant effects were also antagonized by tolazoline. In the absence of 5-HT-induced depression, L-dopa only enhanced transmission through both pathways by inducing release of catecholamines from bulbospinal NE terminals. These results indicate that clonidine depresses sympathetic activity by stimulating inhibitory 5-HT receptors on sympathetic preganglionic neurons, a mechanism that adequately accounts for its central vasodepressor effect.

Management of Fibromyalgia Syndrome: Review of Evidence

Fibromyalgia syndrome (FMS) is a common chronic musculoskeletal pain disorder of unknown etiology and characterized by generalized body pain, hyperalgesia, and other functional and emotional comorbidities. Despite extensive research, no treatment modality is effective for all FMS patients. In this paper, we briefly review the history of FMS and diagnostic criteria, and potential pathophysiological mechanisms including central pain modulation, neurotransmitters, sympatho-adrenal and hypothalamic–pituitary–adrenal systems and peripheral muscle issues. The primary focus of the paper is to review treatment options for managing fibromyalgia symptoms. We will discuss FDA-approved medications and other pharmacologic agents, and non-pharmacologic treatments that have shown promising effects.

Contrasting Effects of Clonidine and 5-Hydroxytryptophan on Spinal Sympathetic Pathways

The effects of clonidine HCI were compared with those of 5-HTP on transmission through two spinal sympathetic pathways, segmental spinal reflex pathways and descending intraspinal excitatory pathways, in unanesthetized spinal cats. Evoked sympathetic discharges were recorded from upper thoracic preganglionic rami. Clonidine (5-50 microgram/kg) produced a parallel, dose-dependent depression of transmission through each pathway. The intraspinal pathway was five time more sensitive than the spinal reflex pathway (ED50s, 6 and 30 microgram/kg), and the spinal reflex pathway could not be depressed by more than 60% even by higher doses. In contrast, 5-HTP was more effective in depressing the spinal reflex than the intraspinal pathway (ED50s 32 and 44 mg/kg), and both pathways could be depressed completely. Small doses of tolazoline or yohimbine rapidly antagonized the effects of clonidine but not 5-HTP. Clonidine and 5-HTP appear to depress the excitability of sympathetic preganglionic neurons by activating alpha2- and 5-HT receptors, respectively. Each mechanism may contribute independently to regulation of the sympathetic outflow.

L-dopa-induced hypotension: depression of spinal sympathetic neurons by release of 5-hydroxytryptamine.

In studies designed to determine the respective functional roles of two bulbospinal monoaminergic pathways to sympathetic preganglionic neurons, both L-dopa and precursors of 5-HT depressed transmission through excitatory spinal reflex and bulbospinal sympathetic pathways. Transmission through spinal reflex pathways was secondarily enhanced after L-dopa. Pharmacological tests indicated mediation of these affects by monoamines. After antagonism or depletion of central 5-HT, L-dopa only enhanced transmission through both pathways. The results indicate that hypotension and other sympathoinhibitory effects of L-dopa are produced at the spinal level by release of 5-HT from terminals of bulbospinal 5-HT pathways that are inhibitory to sympathetic preganglionic neurons. The excitatory effects of L-dopa are apparently mediated by release of catecholamines from bulbospinal noradrenergic pathways that are excitatory.

Management of fibromyalgia syndrome in 2016

Fibromyalgia syndrome is a chronic pain disorder and defies definitively efficacious therapy. In this review, we summarize the results from the early treatment research as well as recent research evaluating the pharmacological, interventional and nonpharmacological therapies. We further discuss future directions of fibromyalgia syndrome management; we specifically focus on the issues that are associated with currently available treatments, such as the need for personalized approach, new technologically oriented and interventional treatments, the importance of understanding and harnessing placebo effects and enhancement of patient engagement in therapy.

Relationship between psychopathology and graduated spinal block findings in chronic pain patients

&NA; The current study was undertaken to investigate the relationship between response to a graduated spinal block and the presence of psychopathology. Subjects consisted of 25 chronic pain patients who had received a graduated spinal block as part of their evaluation. Each was categorized along two dimensions by independent raters based on blind review of hospital records. Dimensions were (1) response to graduated spinal block (appropriate or inappropriate) and (2) presence of clinically significant psychopathology (definitive, probable or none). Results showed that subjects were well distributed across the two dimensions. A 2 × 3 chi‐square comparison failed to show a significant relationship between the two dimensions. However, females and subjects with spontaneous pain onset were found to exhibit significantly more inappropriate responses to spinal blockage. It was concluded that there was no consistent relationship between the presence of psychopathology and response to the graduated spinal block.