Histological, electrophysiological and clinical effects of thermal radiofrequency therapy of the saphenous nerve and pulsed radiofrequency therapy of the sciatic nerve in dogs.

OBJECTIVE: Thermal radiofrequency (TRF) of the saphenous nerve (a sensory nerve) combined with pulsed radiofrequency (PRF) of the sciatic nerve (a sensory and motor nerve) might relieve intractable stifle osteoarthritis (OA) pain in dogs. The objective was to determine if saphenous nerve TRF induces Wallerian degeneration and if sciatic nerve PRF induces degeneration or dysfunction. STUDY DESIGN: Blinded, controlled, randomized, preclinical study. ANIMALS: A group of six intact, female Beagle dogs aged 14-16 months. METHODS: In each dog, one pelvic limb was assigned randomly to the control group and the other to the treatment group. Dogs were anesthetized and, using ultrasonography, radiofrequency electrodes were positioned adjacent to saphenous and sciatic nerves bilaterally; TRF and PRF were performed only in the treatment limb. Motor nerve conduction velocity (MNCV) was measured in both sciatic nerves 2 weeks later, and the dogs were euthanized. Hematoxylin and eosin-stained sections of saphenous and sciatic nerves were examined using light microscopy. Degeneration and inflammation were scored 0 (none) to 3 (severe). A one-tailed, paired Wilcoxon signed-rank test was used to test for differences in scores and MNCV between control and treatment nerves. RESULTS: Degeneration and inflammation scores were higher in treatment saphenous nerves in 5/6 dogs [83%; 95% confidence interval (CI), 36%, 99%]; however, after Bonferroni correction only degeneration score was higher (p = 0.0313). Degeneration, inflammation or decreased MNCV were not observed in sciatic nerves (each outcome: 0/6 nerves, 0%; 95% CI, 0%, 48%). No dogs experienced postprocedural pain or neurological deficits. CONCLUSIONS AND CLINICAL RELEVANCE: The degeneration in TRF-treated saphenous nerves appears sufficient to impair transmission. Sciatic nerve PRF did not cause degeneration with attendant motor deficits, consistent with a proposed neuromodulatory mechanism. A clinical trial is needed to confirm the combined techniques produce analgesia without motor deficits in dogs with stifle OA.

Hyaluronan modulates TRPV1 channel opening, reducing peripheral nociceptor activity and pain.

Hyaluronan (HA) is present in the extracellular matrix of all body tissues, including synovial fluid in joints, in which it behaves as a filter that buffers transmission of mechanical forces to nociceptor nerve endings thereby reducing pain. Using recombinant systems, mouse-cultured dorsal root ganglia (DRG) neurons and in vivo experiments, we found that HA also modulates polymodal transient receptor potential vanilloid subtype 1 (TRPV1) channels. HA diminishes heat, pH and capsaicin (CAP) responses, thus reducing the opening probability of the channel by stabilizing its closed state. Accordingly, in DRG neurons, HA decreases TRPV1-mediated impulse firing and channel sensitization by bradykinin. Moreover, subcutaneous HA injection in mice reduces heat and capsaicin nocifensive responses, whereas the intra-articular injection of HA in rats decreases capsaicin joint nociceptor fibres discharge. Collectively, these results indicate that extracellular HA reduces the excitability of the ubiquitous TRPV1 channel, thereby lowering impulse activity in the peripheral nociceptor endings underlying pain.

Sciatic-femoral nerve block with bupivacaine in goats undergoing elective stifle arthrotomy.

The aim of this study was to describe the sciatic-femoral nerve block (SFNB) in goats and to evaluate the peri-operative analgesia when the goats underwent stifle arthrotomy. The animals were randomly assigned to one of four treatment groups: groups 0.25, 0.5 and 0.75 received 0.25%, 0.5% and 0.75% of bupivacaine, respectively, while group C (control group) received 0.9% NaCl. In all groups, the volume administered was 0.2 mL/kg. Intra-operatively, the proportion of animals receiving rescue propofol was significantly lower in groups 0.5 and 0.75, compared to group C. Post-operatively, the visual analogue scale (VAS) and total pain score were significantly higher in group C than in the other groups. Group 0.75 had the highest percentage of animals showing motor blockade. SFNB performed with bupivacaine resulted in better intra- and post-operative analgesia than SFNB performed with saline. Compared to the other concentrations, 0.5% bupivacaine resulted in satisfactory analgesia with acceptable side effects.

The role of ERK signaling and the P2X receptor on mechanical pain evoked by movement of inflamed knee joint.

Pain during inflammatory joint diseases is enhanced by the generation of hypersensitivity in nociceptive neurons in the peripheral nervous system. To explore the signaling mechanisms of mechanical hypersensitivity during joint inflammation, experimental arthritis was induced by injection of complete Freund's adjuvant (CFA) into the synovial cavity of rat knee joints. As a pain index, the struggle threshold of the knee extension angle was measured. In rats with arthritis, the phosphorylation of extracellular signal-regulated kinase (ERK), induced by passive joint movement, increased significantly in dorsal root ganglion (DRG) neurons innervating the knee joint compared to the naïve rats that received the same movement. The intrathecal injection of a MEK inhibitor, U0126, reduced the phosphorylation of ERK in DRG neurons and alleviated the struggle behavior elicited by the passive movement of the joint. In addition, the injection of U0126 into the joint also reduced the struggle behavior. These findings indicate that the ERK signaling is activated in both cell bodies in DRG neurons and peripheral nerve fibers and may be involved in the mechanical sensitivity of the inflamed joint. Furthermore, the phosphorylated ERK-positive neurons co-expressed the P2X3 receptor, and the injection of TNP-ATP, which antagonizes P2X receptors, into the inflamed joint reduced the phosphorylated ERK and the struggle behavior. Thus, it is suggested that the activation of the P2X3 receptor is involved in the phosphorylation of ERK in DRG neurons and the mechanical hypersensitivity of the inflamed knee joint.

Processing of nociceptive mechanical and thermal information in central amygdala neurons with knee-joint input.

Pain has a strong emotional dimension, and the amygdala plays a key role in emotionality. The processing of nociceptive mechanical and thermal information was studied in individual neurons of the central nucleus of the amygdala, the target of the spino-parabrachio-amygdaloid pain pathway and a major output nucleus of the amygdala. This study is the first to characterize nociceptive amygdala neurons with input from deep tissue, particularly the knee joint. In 46 anesthetized rats, extracellular single-unit recordings were made from 119 central amygdala neurons that were activated orthodromically by electrical stimulation in the lateral pontine parabrachial area and were tested for receptive fields in the knee joints. Responses to brief mechanical stimulation of joints, muscles, and skin and to cutaneous thermal stimuli were recorded. Receptive-field sizes and thresholds were mapped and stimulus-response functions constructed. Neurons in the central nucleus of the amygdala with excitatory input from the knee joint (n = 62) typically had large symmetrical receptive fields in both hindlimbs or in all four extremities and responded exclusively or preferentially to noxious mechanical stimulation of deep tissue (n = 58). Noxious mechanical stimulation of the skin excited 30 of these neurons; noxious heat activated 21 neurons. Stimulus-response data were best fitted by a sigmoid nonlinear regression model rather than by a monotonically increasing linear function. Another 15 neurons were inhibited by noxious mechanical stimulation of the knee joint and other deep tissue. Fifteen neurons had no receptive field in the knee but responded to noxious stimulation of other body areas; 27 nonresponsive neurons were not activated by natural somesthetic stimulation. Our data suggest that excitation is the predominant effect of brief painful stimulation of somatic tissue on the population of central amygdala neurons with knee joint input. Their large symmetrical receptive fields and sigmoid rather than monotonically increasing linear stimulus-response functions suggest a role of nociceptive central amygdala neurons in other than sensory-discriminative aspects of pain.

The surgical anatomy of the stifle joint in sheep.

OBJECTIVE: To provide a detailed description of the surgical anatomy of the stifle joint in sheep. STUDY DESIGN: The results from analysis of cadaveric dissections (14 stifle joints) and stifle radiographs (8 sets of mediolateral and craniocaudal radiographs) are presented. ANIMALS: Skeletally mature ewes of mixed breeds. CONCLUSIONS: Although the anatomy of the ovine stifle joint is similar to that of the human knee joint, a number of unique features were identified. These included the presence of the tendon of the m. extensor digitorum longus on the craniolateral aspect of the stifle joint, the absence of a cranial meniscofemoral ligament (ligament of Humphrey) in the caudal joint space, and attachment of the patellar tendon to the cranial pole of the patella (rather than to the distal pole, as in humans). The implications of these differences are discussed with reference to the suitability of the ovine stifle as a surgical model for the human knee joint.

Innervation of the equine hip and stifle joint capsules.

The hindlimbs of 3 ponies and 3 horses were dissected. The hip joint capsule was found to receive articular nerve fibers from the femoral, obturator, cranial gluteal, and sciatic nerves. The nerve fibers were distributed to the fibrous joint capsule and associated capsular ligaments. The stifle joint capsule was found to receive articular branches from the femoral, saphenous, obturator, common peroneal, and tibial nerves. The fibers terminated in the joint capsule, fat pad, patellar and collateral ligaments, and the internally situated meniscal and cruciate ligaments.