ABSTRACT
Sensitization of primary afferent neurons is one of the most important components of pain hypersensitivity after tissue injury. Insulin-like growth factor 1 (IGF-1), involved in wound repair in injured tissue, also plays an important role in maintaining neuronal function. In the present study, we investigated the effect of tissue IGF-1 on nociceptive sensitivity of primary afferent neurons. Local administration of IGF-1 induced thermal and mechanical pain hypersensitivity in a dose-dependent manner, and was attenuated by IGF-1 receptor (IGF1R) inhibition. Tissue but not plasma IGF-1 levels, as determined by enzyme-linked immunosorbent assay, significantly increased after plantar incision. Immunohistochemistry revealed that IGF1R was predominantly expressed in neurons as well as in satellite glial cells in the dorsal root ganglion (DRG). Double-labeling immunohistochemistry showed that IGF1R expression colocalized with peripherin and TRPV1, but not with NF200 in DRG neurons. The IGF1R inhibitor successfully alleviated mechanical allodynia, heat hyperalgesia, and spontaneous pain behavior observed after plantar incision. Expression of phosphorylated Akt in DRG neurons significantly increased after plantar incision and was suppressed by IGF1R inhibition. These results demonstrate that increased tissue IGF-1 production sensitizes primary afferent neurons via the IGF1R/Akt pathway to facilitate pain hypersensitivity after tissue damage.
Subject(s)
Hyperalgesia/etiology , Hyperalgesia/metabolism , Insulin-Like Growth Factor I/adverse effects , Pain Threshold/physiology , Postoperative Complications/physiopathology , Animals , Cell Count/methods , Disease Models, Animal , Dose-Response Relationship, Drug , Enzyme-Linked Immunosorbent Assay/methods , Ganglia, Spinal/metabolism , Ganglia, Spinal/pathology , Hyperalgesia/drug therapy , Insulin-Like Growth Factor I/metabolism , Male , Oncogene Protein v-akt/metabolism , Pain Measurement , Pain Threshold/drug effects , Podophyllotoxin/analogs & derivatives , Podophyllotoxin/therapeutic use , Postoperative Complications/pathology , Rats , Rats, Sprague-Dawley , Reaction Time/drug effects , Receptor, IGF Type 1/metabolism , Receptor, IGF Type 1/pharmacology , Skin/metabolismABSTRACT
Pro-inflammatory cytokine high mobility group box-1 (HMGB-1) is involved in inflammation in the central nervous system, but less is known about its biological effects in the peripheral nervous system. In the present study, the role of HMGB-1 in the primary afferent nerve was investigated in the context of the pathophysiology of peripheral nerve injury-induced pain hypersensitivity. Real-time PCR confirmed an increase in HMGB-1 mRNA expression in the dorsal root ganglion (DRG) and spinal nerve at 1 day after spinal nerve ligation (SNL). Induction of HMGB-1 mRNA was observed in both injured L5 and uninjured L4. Immunohistochemistry for HMGB-1 revealed that SNL-induced HMGB-1 expression in the primary afferent neurons and satellite glial cells (SGCs) in the DRG, and in Schwann cells in the spinal nerve. Up-regulation of HMGB-1 was associated with translocation of its signal from the nucleus to the cytoplasm. Injection of HMGB-1 into the sciatic nerve produces transient behavioural hyperalgesia. Neutralizing antibody against HMGB-1 successfully alleviated the mechanical allodynia observed after SNL treatment. Receptor for advanced glycation end products (RAGE), one of the major receptors for HMGB-1, was expressed in the primary afferent neurons and SGCs in the DRG, as well as in Schwann cells in the spinal nerve. These results indicate that HMGB-1 is synthesized and secreted into the DRG and spinal nerve, and contributes to the development of neuropathic pain after nerve injury. Blocking HMGB-1/RAGE signalling might thus be a promising therapeutic strategy for the management of neuropathic pain.
Subject(s)
Ganglia, Spinal/metabolism , HMGB1 Protein/biosynthesis , Hyperalgesia/etiology , Hyperalgesia/metabolism , Peripheral Nervous System Diseases/etiology , Peripheral Nervous System Diseases/metabolism , Sciatic Neuropathy/metabolism , Active Transport, Cell Nucleus/physiology , Animals , Disease Models, Animal , Ganglia, Spinal/physiopathology , Gene Expression Regulation/physiology , HMGB1 Protein/administration & dosage , HMGB1 Protein/genetics , HMGB1 Protein/metabolism , Hyperalgesia/physiopathology , Male , Peripheral Nervous System Diseases/physiopathology , Rats , Rats, Sprague-Dawley , Sciatic Neuropathy/physiopathologyABSTRACT
PURPOSE: Radial artery cannulation is a common medical procedure for anesthesia and critical care. To establish the ideal wrist position for radial artery cannulation, we performed ultrasound examinations of the radial artery to investigate the effect of the angle of wrist extension on radial artery dimensions. CLINICAL FEATURES: Measurements were performed in 17 healthy subjects and 17 surgical patients scheduled for coronary artery bypass graft (CABG) surgery. The radial artery was echographically visualized near the styloid process of the radius at the wrist. Radial artery dimensions were measured at wrist joint angles of 0, 15, 30, 45, 60 and 75 degrees . OBSERVATIONS: In both groups, radial artery height was affected by the wrist joint angle. Vessel height was decreased at 60 degrees (one way ANOVA P = 0.027 vs 0 degrees ) and 75 degrees (P < 0.001 vs 0, 15, 45 degrees ) in healthy subject and at 75 degrees in CABG patients (P < 0.001 vs 0 degrees ). The mean differences in radial artery height at 0 and 75 degrees were 0.33 +/- 0.09 mm and 0.20 +/- 0.06 mm for healthy and CABG patients, respectively. Vessel width was not affected by wrist joint angulation up to 75 degrees of extension. CONCLUSION: Our results demonstrate that in healthy subjects, radial artery dimensions are unaltered when the wrist joint is extended up to an angle of 45 degrees . Extension at 60 degrees for healthy subjects and 75 degrees for CABG patients, however, results in a decrease in the height of the radial artery, which could possibly render arterial catheterization more difficult.
