Comparative study of cold hyperalgesia and mechanical allodynia in two animal models of neuropathic pain: different etiologies and distinct pathophysiological mechanisms

Abstract Neuropathic pain (NP) affects more than 8% of the global population. The proposed action of the transient receptor potential ankyrin 1 (TRPA1) as a mechanosensor and the characterization of the transient receptor potential melastatin 8 (TRPM8) as a cold thermosensor raises the question of whether these receptors are implicated in NP. Our study aimed to evaluate the involvement of TRPA1 and TRPM8 in cold and mechanical signal transduction to obtain a comparative view in rat models of streptozotocin-induced diabetes (STZ) and chronic constriction injury of the sciatic nerve (CCI). The electronic von Frey test showed that STZ rats presented mechanical allodynia that was first evidenced on the 14th day after diabetes confirmation, and four days after CCI. This phenomenon was reduced by the intraplantar (ipl) administration of a TRPA1 receptor antagonist (HC-030031; 40 µL/300 µg/paw) in both NP models. Only CCI rats displayed cold hyperalgesia based on the cold plate test. The pharmacological blocking of TRPA1 through the injection of the antagonist attenuated cold hyperalgesia in this NP model. STZ animals showed a reduction in the number of flinches induced by the intraplantar injection of mustard oil (MO; TRPA1 agonist; 0.1%/50 µL/paw), or intraplantar injection of menthol (MT; TRPM8 agonist; 0.5% and 1%/50 µL/paw). The response induced by the ipl administration of MT (1%/50 µL/paw) was significantly different between the CCI and SHAM groups. Together, these data suggest a different pattern in nociceptive behavior associated with different models of NP, suggesting a variant involvement of TRPA1 and TRPM8 in both conditions

Mechanical properties of the sciatic nerve following combined transplantation of analytically extracted acellular allogeneic nerve and adipose-derived mesenchymal stem cells

Purpose To investigate the effects of Chemically Extracted Acellular Nerves (CEANs) when combined with Adipose-Derived mesenchymal Stem Cell (ADSC) transplantation on the repair of sciatic nerve defects in rabbits. Methods A total of 71 six-month-old Japanese rabbit were used in this study. Twenty rabbits served as sciatic nerve donors, while the other 51 rabbits were randomly divided into Autologous Nerve Transplantation Group (ANT, n=17), CEAN group (n=17) and CEAN-ADSCs group (n=17). In all these groups, the rabbits left sciatic nerves were injured before the experiment, and the uninjured sciatic nerves on their right side were used as the control (CON). Electrophysiological tests were carried out and sciatic nerves were prepared for histomorphology and stretch testing at 24 weeks post-transplant. Results There were significant differences between ANT and Con groups in amplitude (AMP): P=0.031; motor nerve conduction velocity (MNCV): P=0.029; Maximum stress: P=0.029; and Maximum strain P=0.027. There were also differences between the CEAN and CEAN+ADSCs groups in AMP: P=0.026, MNCV: P=0.024; Maximum stress: P=0.025 and Maximum strain: P=0.030. No significant differences in these parameters were observed when comparing the ANT and CEAN+SACN groups (MNCV: P=0.071) or the CEAN and ANT groups (Maximum stress: P=0.069; Maximum strain P=0.077). Conclusion Addition of ADSCs has a significant impact on the recovery of nerve function, morphology, and tensile mechanical properties following sciatic nerve injury.(AU)

Unusual relationship between the piriform muscle and sciatic, inferior gluteal and posterior femoral cutaneous nerves / Relación inusual entre el músculo piriforme y los nervios isquiático, glúteo inferior y cutâneo femoral posterior

Piriformis muscle syndrome has been increasingly recognized as a cause of leg pain. Overuse, strain, or anatomical variations of the relationship between the nerve and the piriformis muscle are thought to be the underlying causes of the entrapment of the sciatic nerve. We report a variation not previously described which was found during a routine dissection. During routine dissection of the left gluteal region of an adult male cadaver we observed a high division of the sciatic nerve and the presence of an accessory piriformis muscle. The sciatic nerve divided beneath the piriformis muscle and the common fibular nerve passed over the accessory piriformis muscle, whereas the tibial nerve reflected anteriorly to pass between the accessory piriformis and the superior gemellus muscle. Additionally, both nerves communicated with a side branch under the inferior border of the accessory piriformis muscle and the inferior gluteal nerve originated from the fibular nerve. Anatomical variations in the relationship between the piriformis muscle and the sciatic nerve may be present in up to 17% of the population. Six different variations have been described and none of them is similar to our description. Though complete understanding of the physiopathology of the piriformis muscle syndrome remains to be elucidated, knowledge of the possible anatomical variations may be useful for its adequate diagnosis and treatment.

El síndrome del músculo piriforme se ha reconocido cada vez más como una causa de dolor en los miembros inferiores. Tensión excesiva o variaciones anatómicas del nervio y del músculo piriforme se cree son las causas subyacentes de pinzamiento del nervio isquiático. Se presenta una variación no descrita anteriormente. Durante una disección de rutina en un cadáver de sexo masculino, se observó una división más alta del nervio isquiático y la presencia de un músculo piriforme accesorio. El nervio isquiático se dividía bajo el músculo piriforme y el nervio fibular común pasaba sobre el músculo piriforme accesorio. Por otra parte, el nervio tibial cruzaba entre los músculos piriforme accesorio y gemelo superior. Además, ambos nervios se comunicaban con un ramo lateral bajo el margen inferior del músculo piriforme accesorio y el nervio glúteo inferior se originaba desde el nervio fibular. Variaciones anatómicas y relaciones entre el músculo piriforme y nervio isquiático pueden estar presentes hasta en el 17% de la población. Seis variaciones diferentes se han descrito en este artículo y ninguna es similar a nuestra descripción. A pesar del completo entendimiento de la fisiopatología del síndrome del músculo piriforme, aún queda por esclarecer y conocer las posibles variaciones anatómicas que pueden ser útiles tanto para su diagnóstico como para el tratamiento adecuado.

Bifurcación del nervio ciático a través del músculo piriforme: Hallazgo de un caso / Bifurcation of the ciatic nerve across the piriform muscle: Finding one case

La división inusual del nervio ciático es bastante infrecuente entre la población general. En este artículo se describe la difurcación anormal del nervio ciático derecho en un paciente adulto masculino, además de la perforación del músculo piriforme por el nervio fibular común.

Light and ultrastructural study of sciatic nerve lesions induced using intraneural injection of viable mycobacterium leprae in normal and immunosuppressed swiss white mice

Freshly harvested M. leprae were microinjected into the sciatic nerves of nonimmunosuppressed (non-TR) and immunosuppressed (TR) mice using the technique described by Wisniewski and Bloom. The lesions thus induced, on bypassing the blood-nerve barrier, were biopsied at regular intervals beginning 24 hr and followed up to one year. The fate of M. leprae and the ensuing inflammation and nerve damage were studied using light and electron microscopy. The lesions in both non-TR and TR mice at 24 hr showed an influx of polymorphonuclear leukocytes and an increase in mast cells. The influx and peaking of lymphocytes were delayed by two weeks and 6 weeks, respectively, in TR mice, but the density of lymphocytes at the peak intervals was comparable in both. The plasma cells denoting the humoral response were seen in both, but there was a delay of 3 weeks in non-TR mice. The lesions in non-TR mice showed differentiation of macrophages into epithelioid cells and the formation of giant cells depicting borderline tuberculoid leprosy (BT), Whereas in TR mice, the macrophages showed foamy cytoplasmic changes depicting borderline lepromatous leprosy (BL). Other significant observations common to both non-TR and TR mice were: a) The lesions remained highly localized and showed signs of regression at the 6th and the 12th month intervals. b) The characteristic segmental demyelination and some attempt at remyelination were seen at the site. c) The influx of lymphocytes concorded well with demyelination. d) Bacteria were only seen in the macrophages and never in the Schwann cells or endothelial cells. e) Bacteria persisted in the macrophages, but appeared progressively degenerate at the 6th and 12th post-inoculation months, suggesting loss of viability. The study shows that there was a very effective containment of the infection and that the Schwann cells were resistant to M. leprae infection in the neural milieu. Nerve damage and Schwann cell bacillation do not go hand-in-hand.