Advantages of clamping and drainage over continuous drainage in a total knee arthroplasty.

INTRODUCTION: The use of closed-suction drainage systems after total knee arthroplasty (TKA) is common practice in India, but with no consensus on its use. In this retrospective study, we compared whether clamped or unclamped drainage has any advantages over the other in unilateral TKA. METHODS: Group-A (n = 351) had an unclamped drain removed at 24 h postoperative, with measurement of total drainage at 24 h between January 2011 and February 2013. Group B (n = 349) had drains kept for a total of 8 h-clamped for the first 4 h and unclamped for a further 4, between March 2013 to September 2016. Drainage volume, as well as the hemodynamic markers-hemoglobin (Hb) drop, transfusion rate were evaluated. RESULTS: Mean drain output in Group- A was significantly higher than Group- B (215.64 ml versus 28.34 ml). The postoperative Hb was significantly higher in Group-B (11.46 g/dl versus 10.57 g/dl). Mean Hb drop was significantly higher in Group A (2.16  g/dl versus 1.18 g/dl). The transfusion rates were lower in Group-B, though not statistically significant. CONCLUSIONS: The 4- hour clamping method effectively reduces drain output and fall in hemoglobin. For those who continue using closed suction drains, clamping could prove to be an effective way of reducing post-operative blood loss and the need for transfusions.

First Carpo-metacarpal Joint Arthritis: Interpositional Arthroplasty using Trapezium.

Thumb pain secondary to arthritis at the basal joint of the thumb is a common condition, especially in women, and can be quite disabling. An accurate diagnosis can be readily made from the history and examination. Reconstructive procedures for each stage of the disease are aimed at relieving pain and restoring thumb motion and strength. There are a number of methods available to treat this condition both conservatively and surgically with variable success rates. We present a case of a middle-aged female with first carpo-metacarpal (CMC) joint arthritis in whom we have tried a new technique in which the trapezium is excised, crushed, put in a sponge covering and then inserted back in the void created after excision. At the one-year follow-up, the patient was pain-free and had full range of thumb movement.

Pigmented Villonodular Synovitis of the Knee Joint: A Case Report.

Pigmented villonodular synovitis (PVNS) is a rare, benign, but potentially locally aggressive and recurrent condition characterized by synovial proliferation and hemosiderin deposition inside the joints, tendon sheaths, and bursae. It usually affects the large joints such as hip, knee, and ankle. We report a case of PVNS of the knee joint in a young female which was treated by subtotal synovectomy alone without the use of adjuvants. At the 14-month follow-up, the patient was pain free and had no signs of disease recurrence.

Reconstruction of the Odontoid Process by a Tricortical Iliac Crest Graft in a Case of Tuberculosis of C1, C2, and C3 Vertebrae.

Tuberculosis (TB) is an emerging disease which affects about one-third of the world's population, especially in developing countries. TB of the spine is the most common type of skeletal TB. Cervical spine TB is rare, constituting 2-3% of all cases of spinal TB. We would like to present an unusual case of tuberculosis of the C1, C2, and C3 vertebrae with neurological deficit and its difficult management. A new method of treatment was done for this patient, which included reconstruction of the odontoid process using a tricortical iliac crest graft that was fixed with an anterior cervical plate. On follow-up, there was good incorporation of the graft. The neurological condition of the patient improved and was normal with partial restriction of neck movements. We suggest this technique to be worthwhile for treatment of this disease at this location.

Acute Bilateral Traumatic Achilles Tendon Rupture - A Rare Presentation.

The Achilles tendon is the strongest tendon in the body, which is commonly ruptured in male athletes. Bilateral rupture of the Achilles tendon is a rare condition with very few reported cases in the literature. It poses a challenge in management, and hence, we report a case with traumatic bilateral Achilles tendon rupture in a young male patient and its management. One side was treated conservatively as the rupture was partial and the other side, which had a complete tear, was operated. At nine months follow-up, the patient has had a satisfactory result and is now bearing full weight without any problems. We suggest this method of treatment to be worthwhile for this unusual entity.

Post-traumatic Arthritis of the Tarsometatarsal Joint Complex: A Case Report.

Tarsometatarsal (TMT) arthritis is characterized by instability and pain in the foot. The commonest cause is post-traumatic arthritis. A Lisfranc injury involves the articulation between the medial cuneiform and the base of the second metatarsal, which is considered a keystone to midfoot integrity. Neglected or undertreated injury to the Lisfranc joint complex leads to secondary arthritis and significant disability. We present a case of a young male patient with a two-year-old neglected Lisfranc joint injury and secondary osteoarthritis of the first, second, and fourth TMT joints, which we treated surgically with arthrodesis using screws, with a good functional outcome on final follow-up.

Analysis of outcome of avascular necrosis of femoral head treated by core decompression and bone grafting.

BACKGROUND: Femoral head is the most common bone affected by avascular necrosis. Core decompression procedure, when done in the initial stages, before collapse, may arrest or reverse the progress of avascular necrosis and thereby may preserve the normal femoral head. Hence, we have analysed the clinical, functional and radiological outcome of core decompression and bone grafting in patients with Osteonecrosis of the femoral head (ONFH) upto stage IIB (Ficat & Arlet). MATERIALS AND METHOD: A study was undertaken at our institute from June 2010 to June 2013 wherein 20 patients (28 hips) of ONFH upto grade II B (Ficat & Arlet) were treated with core decompression and the outcomes were studied. Patients were subjected to core decompression of the affected hip. All the patients were operated in lateral position. In 26/28 hips, cancellous grafting was done after harvesting graft from the posterior iliac crest. In 2 patients cortical non-vascularised fibular graft was used. RESULTS: Functional outcome was assessed by Harris hip score, wherein 19 hips (67.85%) had good or excellent outcome; 1 hip (3.57%) had fair out come. However, 8 hips (28.57%) showed poor result. For stage I, 12/13 hips (92.3%) improved, whereas for Stage IIA, 6/11 hips (54.54%) showed improvement and for stage IIB, only 2/4 hips (50%) showed improvement. Less than 25% of the hips required a replacement or salvage procedure. Strict non weight bearing was complied by 23 hips (82.14%), whereas 5 hips (17.85%) were not compliant. If we exclude non compliant patients, our success rate was 92.3% for grade I, 100% for grade IIA and 50% for grade IIB. CONCLUSION: Core decompression and bone grafting provide satisfactory outcome when patients are carefully selected in early stages of the disease, before the stage of collapse.

Endocannabinoid regulation of spinal nociceptive processing in a model of neuropathic pain.

Models of neuropathic pain are associated with elevated spinal levels of endocannabinoids (ECs) and altered expression of cannabinoid receptors on primary sensory afferents and post-synaptic cells in the spinal cord. We investigated the impact of these changes on the spinal processing of sensory inputs in a model of neuropathic pain. Extracellular single-unit recordings of spinal neurones were made in anaesthetized neuropathic and sham-operated rats. The effects of spinal administration of the cannabinoid CB(1) receptor antagonist N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (AM251) and the cannabinoid receptor type 2 (CB(2)) receptor antagonist N-[(1S)-endo-1,3,3-trimethylbicycloheptan-2-yl]-5-(4-chloro-3-methylphenyl)-1-(4-methylbenzyl)-pyrazole-3-carboxamide (SR144528) on mechanically-evoked responses of spinal neurones were determined. The effects of spinal administration of (5Z,8Z11Z,14Z)-N-(3-furanylmethyl)-5,8,11,14-eicosatetraenamide (UCM707), which binds to CB(2) receptors and alters transport of ECs, on evoked responses of spinal neurones and spinal levels of ECs were also determined. The cannabinoid CB(1) receptor antagonist AM251, but not the CB(2) receptor antagonist, significantly facilitated 10-g-evoked responses of spinal neurones in neuropathic, but not sham-operated, rats. Spinal administration of UCM707 did not alter spinal levels of ECs but did significantly inhibit mechanically-evoked responses of neurones in neuropathic, but not sham-operated, rats. Pharmacological studies indicated that the selective inhibitory effects of spinal UCM707 in neuropathic rats were mediated by activation of spinal CB(2) receptors, as well as a contribution from transient receptor potential vanilloid 1 (TRPV1) channels. This work demonstrates that changes in the EC receptor system in the spinal cord of neuropathic rats influence the processing of sensory inputs, in particular low-weight inputs that drive allodynia, and indicates novel effects of drugs acting via multiple elements of this receptor system.

Minocycline treatment inhibits microglial activation and alters spinal levels of endocannabinoids in a rat model of neuropathic pain.

Activation of spinal microglia contributes to aberrant pain responses associated with neuropathic pain states. Endocannabinoids (ECs) are present in the spinal cord, and inhibit nociceptive processing; levels of ECs may be altered by microglia which modulate the turnover of endocannabinoids in vitro. Here, we investigate the effect of minocycline, an inhibitor of activated microglia, on levels of the endocannabinoids anandamide and 2-arachidonoylglycerol (2-AG), and the related compound N-palmitoylethanolamine (PEA), in neuropathic spinal cord. Selective spinal nerve ligation (SNL) in rats resulted in mechanical allodynia and the presence of activated microglia in the ipsilateral spinal cord. Chronic daily treatment with minocycline (30 mg/kg, ip for 14 days) significantly reduced the development of mechanical allodynia at days 5, 10 and 14 post-SNL surgery, compared to vehicle-treated SNL rats (P < 0.001). Minocycline treatment also significantly attenuated OX-42 immunoreactivity, a marker of activated microglia, in the ipsilateral (P < 0.001) and contralateral (P < 0.01) spinal cord of SNL rats, compared to vehicle controls. Minocycline treatment significantly (P < 0.01) decreased levels of 2-AG and significantly (P < 0.01) increased levels of PEA in the ipsilateral spinal cord of SNL rats, compared to the contralateral spinal cord. Thus, activation of microglia affects spinal levels of endocannabinoids and related compounds in neuropathic pain states.

Targeting the cannabinoid system to produce analgesia.

Cannabinoid receptors are present at key sites involved in the relay and modulation of nociceptive responses. The analgesic effects of the cannabinoid CB1 receptor are well described. The widespread distribution of these receptors in the brain does, however, also explain the side-effects associated with CB1 receptor agonists. The cannabinoid CB2 receptor also produces analgesic effects in models of acute, inflammatory and neuropathic pain. The sites and mechanisms of CB2 receptor-mediated analgesia are described herein. In addition to targeting cannabinoid receptors directly, protection of endocannabinoids (eCBs) from metabolism also produces analgesic effects. Indeed, reports that noxious stimulation elevates levels of eCBs in the spinal cord and brain provide further rationale for this approach. The effects of inhibition of fatty acid amide hydrolase (FAAH) on nociceptive responses in models of inflammatory and neuropathic pain are discussed.

Inhibition of fatty acid amide hydrolase and cyclooxygenase-2 increases levels of endocannabinoid related molecules and produces analgesia via peroxisome proliferator-activated receptor-alpha in a model of inflammatory pain.

The antinociceptive effects of the endocannabinoids (ECs) are enhanced by inhibiting catabolic enzymes such as fatty acid amide hydrolase (FAAH). The physiological relevance of the metabolism of ECs by other pathways, such as cyclooxygenase-2 (COX2) is less clear. To address this question we compared the effects of local inhibition of FAAH versus COX2 (URB597 and nimesulide, respectively) on inflammatory hyperalgesia and levels of endocannabinoids and related molecules in the hindpaw. Inflammatory hyperalgesia was measured following intraplantar injection of carrageenan. Effects of intraplantar injection of URB597 (25 microg and 100 microg) or nimesulide (50 microg) on hyperalgesia and hindpaw levels of anandamide (AEA), 2-arachidonoylglycerol (2AG) and N-palmitoylethanolamine (PEA) were determined. Although both doses of URB597 increased levels of AEA and 2AG in the carrageenan inflamed hindpaw, only the lower dose of URB597 attenuated hyperalgesia (P<0.05). Nimesulide attenuated both hyperalgesia and hindpaw oedema (P<0.001, P<0.01, respectively) and increased levels of PEA (P<0.05) in the hindpaw. Since both AEA and PEA are ligands for peroxisome proliferator-activated receptor-alpha (PPARalpha), the effects of the PPARalpha antagonist GW6471 on nimesulide- and URB597-mediated effects were studied. GW6471, but not a PPARgamma antagonist, blocked the inhibitory effects of nimesulide and URB597 on hyperalgesia. Our data suggest that both COX2 and FAAH play a role in the metabolism of endocannabinoids and related molecules. The finding that PPARalpha antagonism blocked the inhibitory effects of nimesulide and URB597 suggests that PPARalpha contributes to their antinociceptive effects in the carrageenan model of inflammatory hyperalgesia.

Cannabinoid CB2 receptor-mediated anti-nociception in models of acute and chronic pain.

The endocannabinoid system consists of cannabinoid CB(1) and CB(2) receptors, endogenous ligands and their synthesising/metabolising enzymes. Cannabinoid receptors are present at key sites involved in the relay and modulation of nociceptive information. The analgesic effects of cannabinoids have been well documented. The usefulness of nonselective cannabinoid agonists can, however, be limited by psychoactive side effects associated with activation of CB(1) receptors. Following the recent evidence for CB(2) receptors existing in the nervous system and reports of their up-regulation in chronic pain states and neurodegenerative diseases, much research is now aimed at shedding light on the role of the CB(2) receptor in human disease. Recent studies have demonstrated anti-nociceptive effects of selective CB(2) receptor agonists in animal models of pain in the absence of CNS side effects. This review focuses on the analgesic potential of CB(2) receptor agonists for inflammatory, post-operative and neuropathic pain states and discusses their possible sites and mechanisms of action.

Analgesic effects of fatty acid amide hydrolase inhibition in a rat model of neuropathic pain.

Cannabinoid-based medicines have therapeutic potential for the treatment of pain. Augmentation of levels of endocannabinoids with inhibitors of fatty acid amide hydrolase (FAAH) is analgesic in models of acute and inflammatory pain states. The aim of this study was to determine whether local inhibition of FAAH alters nociceptive responses of spinal neurons in the spinal nerve ligation model of neuropathic pain. Electrophysiological studies were performed 14-18 d after spinal nerve ligation or sham surgery, and the effects of the FAAH inhibitor cyclohexylcarbamic acid 3-carbamoyl biphenyl-3-yl ester (URB597) on mechanically evoked responses of spinal neurons and levels of endocannabinoids were determined. Intraplantar URB597 (25 microg in 50 microl) significantly (p < 0.01) attenuated mechanically evoked responses of spinal neurons in sham-operated rats. Effects of URB597 were blocked by the cannabinoid 1 receptor (CB1) antagonist AM251 [N-1-(2,4-dichlorophenyl)-5-(4-iodophenyl)-4-methyl-N-1-piperidinyl-1H-pyrazole-3-carboxamide] (30 microg in 50 microl) and the opioid receptor antagonist naloxone. URB597 treatment increased levels of anandamide, 2-arachidonyl glycerol, and oleoyl ethanolamide in the ipsilateral hindpaw of sham-operated rats. Intraplantar URB597 (25 microg in 50 microl) did not, however, alter mechanically evoked responses of spinal neurons in spinal nerve ligated (SNL) rats or hindpaw levels of endocannabinoids. Intraplantar injection of a higher dose of URB597 (100 microg in 50 microl) significantly (p < 0.05) attenuated evoked responses of spinal neurons in SNL rats but did not alter hindpaw levels of endocannabinoids. Spinal administration of URB597 attenuated evoked responses of spinal neurons and elevated levels of endocannabinoids in sham-operated and SNL rats. These data suggest that peripheral FAAH activity may be altered or that alternative pathways of metabolism have greater importance in SNL rats.

Inhibition of peripheral vanilloid TRPV1 receptors reduces noxious heat-evoked responses of dorsal horn neurons in naïve, carrageenan-inflamed and neuropathic rats.

The vanilloid TRPV1 receptor, present on primary afferent fibres, is activated by noxious heat, low pH and endogenous vanilloids. Changes in the function or distribution of TRPV1 receptors may play an important role in pain induced by inflammation or neuropathy. The aim of the present study was to evaluate the role of peripheral TRPV1 receptors in thermal nociception in rat models of inflammatory and neuropathic pain. Here, we have determined the effects of peripheral administration of the potent TRPV1 receptor antagonist iodoresiniferatoxin (IRTX) on noxious heat (45 degrees C)-evoked responses of spinal wide dynamic range (WDR) neurons in naïve, carrageenan-inflamed, sham-operated and L5/6 spinal nerve-ligated (SNL) anaesthetized rats in vivo. In addition, effects of peripheral administration of IRTX on mechanically evoked responses of WDR neurons were determined in sham-operated and SNL rats. Carrageenan inflammation significantly (P<0.05) increased the 45 degrees C-evoked responses of WDR neurons. Intraplantar injection of the lower dose of IRTX (0.004 microg) inhibited (P<0.05) 45 degrees C-evoked responses of WDR neurons in carrageenan-inflamed, but not in naïve, rats. The higher dose of IRTX (0.4 microg) significantly (P<0.05) inhibited 45 degrees C-evoked responses in both inflamed and naïve rats. In sham-operated and SNL rats, IRTX (0.004 and 0.4 microg) significantly (P<0.05) inhibited 45 degrees C-evoked, but had no effect on mechanically evoked responses of WDR neurons. These data support the role of peripheral TRPV1 receptors in noxious thermal transmission in naïve, inflamed and neuropathic rats, and suggest that there is an increased functional contribution of peripheral TRPV1 receptors following acute inflammation.

Cannabinoid CB2 receptor activation inhibits mechanically evoked responses of wide dynamic range dorsal horn neurons in naïve rats and in rat models of inflammatory and neuropathic pain.

Peripheral cannabinoid 2 receptors (CB2 receptors) modulate immune responses and attenuate nociceptive behaviour in models of acute and persistent pain. The aim of the present study was to investigate whether peripheral CB2 receptors modulate spinal processing of innocuous and noxious responses and to determine whether there are altered roles of CB2 receptors in models of persistent pain. Effects of local administration of the CB2 receptor agonist JWH-133 (5 and 15 microg/50 microL) on mechanically evoked responses of spinal wide dynamic range (WDR) neurons in noninflamed rats, rats with carrageenan-induced hindpaw inflammation, sham operated rats and spinal nerve-ligated (SNL) rats were determined in anaesthetized rats in vivo. Mechanical stimulation (von Frey filaments, 6-80 g) of the peripheral receptive field evoked firing of WDR neurons. Mechanically evoked responses of WDR neurons were similar in noninflamed, carrageenan-inflamed, sham-operated and SNL rats. Intraplantar injection of JWH-133 (15 microg), but not vehicle, significantly (P < 0.05) inhibited innocuous and noxious mechanically evoked responses of WDR neurons in all four groups of rats. In many cases the selective CB2 receptor antagonist, SR144528 (10 microg/50 microL), attenuated the inhibitory effects of JWH-133 (15 microg) on mechanically evoked WDR neuronal responses. The CB1 receptor antagonist, SR141716A, did not attenuate the inhibitory effects of JWH-133 on these responses. Intraplantar preadministration of JWH-133 also inhibited (P < 0.05) carrageenan-induced expansion of peripheral receptive fields of WDR dorsal horn neurons. This study demonstrates that activation of peripheral CB2 receptors attenuates both innocuous- and noxious-evoked responses of WDR neurons in models of acute, inflammatory and neuropathic pain.

Cannabinoids modulate ultrasound-induced aversive responses in rats.

RATIONALE: Mechanisms and brain substrates mediating cannabinoid-induced modulation of behaviour towards aversive stimuli are poorly understood. OBJECTIVES: To investigate the effects of systemic and intra-dorsal periaqueductal grey (PAG) administration of the cannabinoid receptor agonist HU210 on behaviour and plasma corticosterone levels in rats exposed to ultrasound and determine the contribution of CB(1) receptors. METHODS: In experiment 1, rats received vehicle or CB(1) receptor antagonist SR141716A (3 mg/kg, IP) 30 min prior to a second injection of vehicle or HU210 (5, 20 or 80 microg/kg, IP). In experiment 2, rats received intra-dorsal PAG vehicle or SR141716A (30 microg/rat) 10 min prior to intra-dorsal PAG vehicle or HU210 (5 microg/rat). Following injections, rats were exposed to an aversive 20 kHz ultrasonic tone for 3 min. Behaviour, including hyperlocomotor activity and freezing, was monitored during and post-ultrasound. Plasma corticosterone levels 10 min post-ultrasound were measured. RESULTS: Ultrasound induced explosive running and freezing behaviour. Systemic administration of HU210 attenuated the expression of ultrasound-induced hyperlocomotor activity and increased freezing. The HU210-induced attenuation of hyperlocomotor activity was blocked by SR141716A. Intra-PAG administration of HU210 reduced the expression of ultrasound-induced hyperlocomotor activity, an effect not blocked by SR141716A. Systemic and intra-PAG administration of HU210 increased plasma corticosterone levels, an effect not blocked by SR141716A. CONCLUSIONS: The cannabinoid receptor agonist HU210 modulates behaviour towards an aversive ultrasound stimulus in rats, an effect accompanied by increased HPA axis activity. These effects may be mediated, at least in part, by the dorsal PAG but cannot be explained solely by an action at CB(1) receptors.

Activation of peripheral cannabinoid CB1 receptors inhibits mechanically evoked responses of spinal neurons in noninflamed rats and rats with hindpaw inflammation.

The presence of cannabinoid1 (CB1) receptors on primary afferent fibres may provide a novel target for cannabinoid analgesics. The present study investigated the ability of peripheral CB1 receptors to modulate innocuous and noxious transmission in noninflamed rats and rats with peripheral carrageenan inflammation. Effects of peripheral injection of arachidonyl-2-choroethylamide (ACEA; 10 and 30 micro g in 50 micro L), a selective CB1 receptor agonist, on mechanically evoked responses of dorsal horn neurons were studied in noninflamed rats and rats with peripheral carrageenan inflammation. Peripheral injection of ACEA (30 micro g in 50 micro L) significantly inhibited innocuous (12 g) mechanically evoked responses of spinal neurons in noninflamed (27 +/- 4% of control; P < 0.01) and inflamed (12 +/- 8% of control; P < 0.05) rats. Similarly, noxious (80 g) mechanically evoked responses of spinal neurons were inhibited by peripheral injection of ACEA (30 micro g in 50 micro L) in noninflamed rats (51 +/- 9% of control; P < 0.01) and rats with peripheral carrageenan inflammation (21 +/- 8% of control; P < 0.01). Inhibitory effects of ACEA were significantly greater in rats with peripheral carrageenan inflammation than in noninflamed rats (P < 0.05). Inhibitory effects of ACEA were significantly blocked by coadministration of the CB1 receptor antagonist SR141716A in both groups of rats. Peripheral injection of SR141716A alone did not alter mechanically evoked responses of spinal neurons in either group of rats. These data demonstrate that activation of peripheral CB1 receptors can inhibit innocuous and noxious somatosensory processing. Furthermore, following peripheral inflammation there is an enhanced inhibitory effect of a peripherally administered CB1 receptor agonist on both innocuous and noxious mechanically evoked responses of spinal neurons.

The role of the central nucleus of the amygdala in nociception and aversion.

The role of the central nucleus of the amygdala in nociception--conditioned and unconditioned aversion--was studied. Rats received microinjection of vehicle or the N-type Ca2+ channel blocker omega-conotoxin GVIA (0.2 microg/250 nl) into the central amygdaloid nucleus prior to intra-plantar injection of formalin, ultrasound exposure or immediately prior to the acquisition phase of an aversive conditioning trial. Intra-amygdala omega-conotoxin GVIA resulted in an earlier onset of nociceptive response to formalin and increased nociceptive behaviour during the first 5 min. Omega-conotoxin GVIA significantly reduced conditioned freezing behaviour with no effect on ultrasound-induced unconditioned aversive behaviour. These data indicate that N-type Ca2+ channels in the central amygdaloid nucleus play a role in mediating behavioural responses to nociceptive and conditioned aversive stimuli.