Inflammation induces α-adrenoceptor expression in peripheral blood mononuclear cells of patients with complex regional pain syndrome.

Persistent regional and systemic inflammation may promote pain and hyperalgesia in complex regional pain syndrome (CRPS). In this study, we investigated whether stimulation of α-adrenoceptors (α-AR) on peripheral blood mononuclear cells (PBMC) might contribute to this inflammatory state. PBMC were isolated from venous blood collected from 21 CRPS patients and 21 sex and age-matched controls.

Olfaction in Complex Regional Pain Syndrome.

Objective: Complex regional pain syndrome (CRPS) is associated with a range of sensory disturbances on the symptomatic side of the body but whether this includes olfaction is uncertain. To clarify this, the aims of this study were to compare ratings of intensity and hedonic appeal of household odorants in CRPS patients and controls, and to determine whether ratings differed between the symptomatic and contralateral sides within the sample of patients.

Methods: Six odorants (vanilla, fish sauce, vinegar, eucalyptus, almond essence and acetone) were presented sequentially in random order on cottonwool buds held in the midline approximately 1 cm from both nostrils in 37 CRPS patients and 21 pain-free controls.

Auditory disturbances in patients with complex regional pain syndrome.

Complex regional pain syndrome (CRPS) is often associated with reduced sound tolerance (hyperacusis) on the affected side, but the mechanism of this symptom is unclear. As compensatory increases in central auditory activity after cochlear injury may trigger hyperacusis, hearing and discomfort thresholds to pure tones (250, 500, 1000, 2000, 3000, 4000, 6000, and 8000 Hz) were assessed in 34 patients with CRPS and 26 pain-free controls. In addition, in 31 patients and 17 controls, auditory-evoked potentials to click stimuli (0.

Stimulation of alpha-1 adrenoceptors may intensify cutaneous inflammation in complex regional pain syndrome.

Alpha-1 adrenoceptors are overexpressed in the epidermis of a subgroup of patients with complex regional pain syndrome (CRPS). Activating α 1 -adrenoceptors in epidermal cells increases production of the proinflammatory cytokine interleukin-6 (IL-6), a mediator of inflammation. To investigate whether this might exacerbate inflammation in CRPS, primary keratinocytes or dermal fibroblasts were cultured from skin biopsies obtained from the affected limb of 25 patients and a similar site in 28 controls.

Co-morbidity between trigeminal autonomic cephalalgias and complex regional pain syndrome: Two case reports.

Background: Trigeminal autonomic cephalalgias and complex regional pain syndrome are rare conditions, and their co-occurrence has not been reported previously. In two patients, ipsilateral trigeminal autonomic cephalalgias developed after the onset of upper limb complex regional pain syndrome. Hyperalgesia to thermal and mechanical stimuli extended beyond the affected limb to encompass the ipsilateral forehead, and was accompanied by ipsilateral hyperacusis and photophobia.

Pupillary Reflexes in Complex Regional Pain Syndrome: Asymmetry to Arousal Stimuli Suggests an Ipsilateral Locus Coeruleus Deficit.

Converging lines of evidence suggest that autonomic and nociceptive pathways linked with the locus coeruleus are disrupted in complex regional pain syndrome (CRPS). To investigate this, pupillary dilatation to arousal stimuli (which reflects neural activity in the locus coeruleus) and pupillary reflexes to light were assessed in a cross-sectional study of 33 patients with CRPS. Moderately painful electrical shocks were delivered to the affected or contralateral limb and unilateral 110 dB SPL acoustic startle stimuli were delivered via headphones.

The Source of Hemisensory Disturbances in Complex Regional Pain Syndrome.

Objectives: In complex regional pain syndrome (CRPS), sensory deficits and/or hyperalgesia often extend beyond the affected limb to encompass other sites on the ipsilateral side of the body. The aim of this study was to determine whether hyperalgesia in the ipsilateral forehead reflects disinhibition and/or sensitization of trigeminal afferent or second-order neurons on the CRPS-affected side.

Participants And Methods: To investigate this, blink reflexes to supraorbital electrical stimuli (a 2 mA triple pulse delivered using a concentric electrode) were recorded bilaterally in 30 CRPS patients and 20 controls of similar age and sex distribution.

Photophobia in complex regional pain syndrome: visual discomfort is greater on the affected than unaffected side.

In complex regional pain syndrome (CRPS), hyperalgesia encompasses uninjured sites on the ipsilateral side of the body and may also include the special senses because auditory discomfort often is greater on the CRPS-affected side. To determine whether this hemilateral hyperalgesia involves the visual system, the discomfort threshold to a light-source that increased in intensity at 100 lux/second from 500 to 3600 lux was investigated for each eye, and the nasal and temporal half of each visual field, in 33 patients with CRPS and 21 pain-free controls. Recent headache history was reviewed and, in patients with CRPS, sensitivity to mechanical and thermal stimuli was assessed in all 4 limbs and on each side of the forehead.

Parallels between lumbosacral radiculopathy and complex regional pain syndrome: α1-adrenoceptor upregulation, reduced dermal nerve fibre density, and hemisensory disturbances in postsurgical sciatica.

Residual lower-limb pain after low back surgery (postsurgical sciatica) and complex regional pain syndrome (CRPS) involving a lower limb are separate conditions but may share some mechanisms (eg, tissue inflammation, neuroimmune disturbances, and central neuroplasticity). As adrenergically evoked pain contributes, in part, to CRPS, whether an adrenergic mechanism also contributes to postsurgical sciatica was investigated in this study. Immunohistochemistry was used to identify α1-adrenoceptors (α1-AR) on nerve fibres and other targets in the affected and contralateral skin of 25 patients with postsurgical sciatica, and α1-AR expression was investigated in relation to pain and pinprick hyperalgesia after intradermal injection of the α1-AR agonist phenylephrine.

Expression of Cutaneous Beta-2 Adrenoceptors Is Similar in Patients with Complex Regional Pain Syndrome and Pain-Free Controls.

Objective: Studies in rodents suggest that cutaneous beta-2 adrenoceptors (β2-ARs) mediate inflammation and pain after tissue injury and that inflammation and peripheral nerve injury trigger increases in neuronal β2-AR expression. Hence, the aim of this study was to investigate the expression of β2-ARs on keratinocytes and dermal nerves in patients with complex regional pain syndrome (CRPS).

Design, Setting, And Subjects: Fifty-eight patients with CRPS were recruited for this study.

Complex regional pain syndrome: intradermal injection of phenylephrine evokes pain and hyperalgesia in a subgroup of patients with upregulated α1-adrenoceptors on dermal nerves.

The aim of this study was to determine whether upregulated cutaneous expression of α1-adrenoceptors (α1-AR) is a source of pain in patients with complex regional pain syndrome (CRPS). Immunohistochemistry was used to identify α1-AR on nerve fibres and other targets in the affected and contralateral skin of 90 patients, and in skin samples from 38 pain-free controls. The distribution of α1-AR was compared between patients and controls, and among subgroups of patients defined by CRPS duration, limb temperature asymmetry, and diagnostic subtype (CRPS I vs CRPS II).

Dermal nerve fibre and mast cell density, and proximity of mast cells to nerve fibres in the skin of patients with complex regional pain syndrome.

An interaction between cutaneous nerves and mast cells may contribute to pain in complex regional pain syndrome (CRPS). To explore this, we investigated the density of dermal nerve fibres, and the density and proximity of mast cells to nerve fibres, in skin biopsies obtained from the affected and unaffected limbs of 57 patients with CRPS and 28 site-matched healthy controls. The percentage of the dermis stained by the pan-neuronal marker protein gene-product 9.

Hemisensory disturbances in patients with complex regional pain syndrome.

Sensory disturbances often spread beyond the site of injury in complex regional pain syndrome (CRPS) but whether this applies equally to CRPS I and II, or changes across the course of the disease, is unknown. Establishing this is important, because different symptom profiles in CRPS I and II, or in acute vs chronic CRPS, might infer different pathophysiology and treatment approaches. To explore these questions, sensory disturbances were assessed in the limbs and forehead of 71 patients with CRPS I and 33 patients with CRPS II.

Hyperacusis in chronic pain: neural interactions between the auditory and nociceptive systems.

Objective: Sensory disturbances are common in chronic pain patients. Hyperacusis can be an especially debilitating experience. Here, we review published work on how the auditory and nociceptive systems might interact in chronic pain syndromes to produce pain-hyperacusis.

Topical prazosin attenuates sensitivity to tactile stimuli in patients with complex regional pain syndrome.

Background: The sympathetic nervous system may play an important role in certain forms of chronic pain. The main aim of this study was to determine whether functional blockade of α1 -adrenoceptors would alter sensitivity to cutaneous stimulation in patients with complex regional pain syndrome (CRPS).

Methods And Results: In an initial study, high-performance liquid chromatography-mass spectrometry of intradermal interstitial fluid collected from the forearms of three healthy individuals established that the α1 -adrenoceptor antagonist prazosin penetrated the skin barrier when mixed in Lipoderm(®) cream base.

Topical treatment in pain medicine: from ancient remedies to modern usage.

Over several millennia, substances have been applied to the skin for treatment of pain. Some ingredients are in current use; others have been discontinued. Mechanisms of action include interactions with nociceptive neural networks and inflammatory processes.

Up-regulation of cutaneous α1-adrenoceptors after a burn.

Stimulation of α1-adrenoceptors evokes inflammatory cytokine production, boosts neurogenic inflammation and pain, and influences cellular migration and proliferation. As expression of α1-adrenoceptors increases on dermal nerves and keratinocytes after peripheral nerve injury, the aim of this study was to determine whether another form of tissue injury (a cutaneous burn) triggered a similar response. In particular, changes in expression of α1-adrenoceptors were investigated on dermal nerve fibres, keratinocytes and fibroblast-like cells using immunohistochemistry 2-12 weeks after a full thickness burn in Wistar rats.

Up-regulation of cutaneous α1 -adrenoceptors in complex regional pain syndrome type I.

Background: In a small radioligand-binding study of cutaneous α1 -adrenoceptors in complex regional pain syndrome (CRPS), signal intensity was greater in the CRPS-affected limb than in controls. However, it was not possible to localize heightened expression of α1 -adrenoceptors to nerves, sweat glands, blood vessels, or keratinocytes using this technique.

Methods: To explore this in the present study, skin biopsies were obtained from 31 patients with CRPS type I and 23 healthy controls of similar age and sex distribution.

Effects of testosterone treatment on bone mineral density in hypogonadal men receiving intrathecal opioids.

Background: Opioid induced depression of sex hormones is a common finding in chronic pain patients receiving long-term opioids by oral, parenteral and even intrathecal routes of administration. The hypothalamic suppression by opioids leads to a hypogonadal state with low testosterone levels in males and subsequent low bone mineral density (BMD).

Methods: We have studied the effects of intrathecally administered opioids on BMD in a group of male chronic pain patients.

Activation of cutaneous immune responses in complex regional pain syndrome.

Unlabelled: The pathogenesis of complex regional pain syndrome (CRPS) is unresolved, but tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) are elevated in experimental skin blister fluid from CRPS-affected limbs, as is tryptase, a marker for mast cells. In the rat fracture model of CRPS, exaggerated sensory and sympathetic neural signaling stimulate keratinocyte and mast cell proliferation, causing the local production of high levels of inflammatory cytokines leading to pain behavior. The current investigation used CRPS patient skin biopsies to determine whether keratinocyte and mast cell proliferation occur in CRPS skin and to identify the cellular source of the up-regulated TNF-α, IL-6, and tryptase observed in CRPS experimental skin blister fluid.

Upregulation of α1-adrenoceptors on cutaneous nerve fibres after partial sciatic nerve ligation and in complex regional pain syndrome type II.

After peripheral nerve injury, nociceptive afferents acquire an abnormal excitability to adrenergic agents, possibly due to an enhanced expression of α1-adrenoceptors (α1-ARs) on these nerve fibres. To investigate this in the present study, changes in α1-AR expression on nerve fibres in the skin and sciatic nerve trunk were assessed using immunohistochemistry in an animal model of neuropathic pain involving partial ligation of the sciatic nerve. In addition, α1-AR expression on nerve fibres was examined in painful and unaffected skin of patients who developed complex regional pain syndrome (CRPS) after a peripheral nerve injury (CRPS type II).

Increased expression of cutaneous α1-adrenoceptors after chronic constriction injury in rats.

Unlabelled: α1-Adrenoceptor expression on nociceptors may play an important role in sympathetic-sensory coupling in certain neuropathic pain syndromes. The aim of this study was to determine whether α1-adrenoceptor expression was upregulated on surviving peptidergic, nonpeptidergic, and myelinated nerve fiber populations in the skin after chronic constriction injury of the sciatic nerve in rats. Seven days after surgery, α1-adrenoceptor expression was upregulated in the epidermis and on dermal nerve fibers in plantar skin ipsilateral to the injury but not around blood vessels.

A disturbance in sensory processing on the affected side of the body increases limb pain in complex regional pain syndrome.

Objectives: The aim of this study was to determine whether a central disturbance in somatosensory processing contributes to limb pain in complex regional pain syndrome (CRPS).

Methods: In 37 patients with CRPS, the effect of cooling the ipsilateral forehead on pain in the affected limb was compared with the effect of cooling the contralateral forehead. In addition, symptoms associated with cold-evoked limb pain were explored.