The journal of pain : official journal of the American Pain Society
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The aim of this study was to investigate local opioid effects in the inflamed skin of healthy human volunteers. To induce inflammation, the circular tip of a 10-mm-diameter probe was heated to 48 degrees C and applied for 120 seconds to a site on each forearm of 24 healthy participants. Thirty minutes later, 0.2 mL of normal saline was injected subcutaneously into 1 inflamed site, and the opioid antagonist naloxone hydrochloride (80 microg in 0.2 mL) was injected subcutaneously into the other inflamed site. Participants completed tests of pain sensitivity (heat pain thresholds, heat pain ratings, and mechanical pain ratings) before and after the injections. Fentanyl citrate (10 microg in 0.2 mL) was then injected into the pretreated sites, and pain sensitivity was measured again. The thermal injuries produced thermal and mechanical hyperalgesia that did not differ between the saline and naloxone sites. After the fentanyl injections, decreases in thermal and mechanical hyperalgesia were greater at the saline site than the naloxone site. These findings demonstrate that pretreatment with naloxone blocks local opioid effects produced by the subcutaneous injection of a low dose of fentanyl in the inflamed skin of healthy humans. Thus, peripheral opioid receptors could be a therapeutic target for painful cutaneous disorders. ⋯ This article demonstrates that activation of opioid receptors in the skin inhibits sensitivity to painful mechanical and thermal stimuli. Thus, local application of low-dose opioid medications could relieve painful skin disorders.
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Characteristics of sensory dorsal root ganglia (DRG) neurons innervating the L5 vertebral body were investigated in rats by using a retrograde neurotransport method, lectin affinity- and immuno-histochemistry to further elucidate the causes of diffuse pain suffered by some elderly patients in their back, lateral trunk, and iliac crest, after lumbar osteoporotic vertebral fracture. We used calcitonin gene-related peptide (CGRP) as a marker of small peptide-containing neurons and the glycoprotein binding the isolectin from Griffonia simplicifolia (IB4) as a marker of small non-peptide-containing neurons. Neurons innervating the L5 vertebral bodies, retrogradely labeled with fluoro-gold (FG), were distributed throughout DRGs from T13 to L6. The proportion of CGRP-immunoreactive (IR) FG-labeled neurons was 32%. The proportion of IB4-binding FG-labeled neurons was significantly smaller, at 4%. Other neurons that were non-CGRP-IR and non-IB4-binding were mostly large neurons, and they may transmit proprioception from vertebral bodies. Most neurons transmitting pain are CGRP-IR peptide-containing neurons. They may have a more significant role in pain sensation in the vertebral bodies as peptidergic DRG neurons. ⋯ This article shows that vertebral bodies are innervated by CGRP-IR neurons. CGRP-IR neurons may play a role in pain sensation through peptidergic DRG neurons. These findings contribute to an understanding of pain associated with the vertebral body such as tumor, infection, or osteoporotic fracture.
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The aim of this study was to examine whether gastric afferent information converged onto upper thoracic spinal neurons that received noxious cardiac input. Extracellular potentials of single upper thoracic (T3) spinal neurons were recorded in pentobarbital-anesthetized, paralyzed, ventilated male rats. Gastric distension (GD) (20, 40, 60 mm Hg, 20 seconds) was produced by air inflation of a latex balloon surgically placed in the stomach. A catheter was placed in the pericardial sac to administer bradykinin solution (10 microg/mL, 0.2 mL, 1 minute) as a noxious cardiac stimulus. Noxious GD (> or =40 mm Hg) altered activity of 26 of 31 (84%) spinal neurons receiving cardiac input. Twenty-two (85%) gastrocardiac convergent neurons were excited, and 1 neuron was inhibited by both intrapericardial bradykinin and GD; the remainder exhibited biphasic response patterns. Twenty-three of 26 (88%) gastrocardiac neurons also received convergent somatic input from the chest, triceps, and upper back areas. Bilateral cervical vagotomy did not significantly affect excitatory responses to GD in 5 of 5 neurons tested. Spinal transection at the C1 segment after vagotomy did not affect excitatory responses to GD in 3 of 4 neurons but abolished the GD response in 1 neuron. These data showed that a gastric stimulus excited T3 spinal neurons with noxious cardiac input primarily by way of intraspinal ascending pathways. ⋯ Convergence of gastric afferent input onto upper thoracic spinal neurons receiving noxious cardiac input that was observed in the present study may provide a spinal mechanism that explains stomach-heart cross-organ communication, such as postprandial triggering and worsening of angina pectoris in patients with coronary artery disease.