Co-existence of the double inferior vena cava with complex interiliac venous communication and aberrant common hepatic artery arising from superior mesenteric artery: a case report.

Variations of the arterial and venous system of the abdomen and pelvis have important clinical significance in hepatobiliary surgery, abdominal laparoscopy, and radiological intervention. A case of double inferior vena cava (IVC) with complex interiliac communication and variation of the common hepatic artery (CHA) arising from superior mesenteric artery (SMA) in a 79-year-old male cadaver is presented. Both IVCs ascended on either side of the abdominal aorta. The left-sided IVC crossed anterior to the aorta at the level of the left renal vein. The union of both IVCs was at the level just above the right renal vein. The diameter of right-sided IVC, left-sided IVC and the common IVC were 16.73 mm, 21.57 mm and 28.75 mm, respectively. In the pelvic cavity, the right common iliac vein was formed by a union of right external and internal iliac veins while the formation of left common iliac vein was from the external iliac vein and two internal iliac veins. An interiliac vein ran from right internal iliac vein to left common iliac vein with an additional communicating vein running from the middle of this interiliac vein to the right common iliac vein. Another co-existence variation in this case was the origin of the CHA arising from the SMA with a suprapancreatic retroportal course. Clinical importance of double IVC are observed in retroperitoneal surgery, whole organ transplantation or radical nephrectomy, surgical ligation of the IVC or the placement of an IVC filter for thromboembolic disease. The variation of CHA has an important clinical significance in liver transplantation, abdominal laparoscopy and radiological abdominal intervention. (Folia Morphol 2018; 77, 1: 151-155).

Multiple variations in the course and motor branching pattern of the musculocutaneous nerve with unusual communication with the median nerve.

Anatomic variations in course and motor branching pattern of the musculocutaneous nerve (MCN) with unusual communication with the median nerve were determined on the left arm of a 62-year-old formalin fixed male cadaver. The MCN did not pierce the coracobrachialis muscle. It provided 4 primary motor branches. The first branch emerged 1.5 cm inferior to the coracoid process to innervate the coracobrachialis muscle. The second branch emerged 8 cm inferior to the coracoid process to innervate the biceps brachii muscle. The third branch to brachialis muscle emerged 13.9 cm inferior to the coracoid process. The last branch to the common belly of biceps brachii muscle emerged 19.6 cm inferior to the coracoid process. Two communications with the median nerve were observed. The proximal thick communicating branch had the direction from the MCN to the median nerve while the distal one was a small nerve bundle with a direction from the median nerve to the MCN. The present report provided evidence of multiple variations in one MCN which had not been reported previously. Anatomic variation in this case has clinical implications, considering that injury of the MCN in the upper part of arm would cause unexpected paralysis of flexor muscles of forearm and thenar muscle due to communications between this and median nerve.

Curcumin reduces blood-nerve barrier abnormalities and cytotoxicity to endothelial cells and pericytes induced by cisplatin.

BACKGROUND: Cisplatin is a platinum-based antineoplastic agent used to treat cancers of solid organs. Neuropathy is one of its major side effects, necessitating dose reduction or cessation. Previous studies suggested that cisplatin causes microvascular toxicity, including pericyte detachment. This study aimed to clarify whether these alterations occurred in the blood-nerve barrier (BNB) of capillaries after cisplatin treatment. MATERIALS AND METHODS AND RESULTS: Electron microscopic analysis of rat sciatic nerves with cisplatin neuropathy showed increased frequency and severity of pericyte detachment. Moreover, the vascular basement membrane did not tightly encircle around the endothelial cells and pericytes. Cultured human umbilical vein endothelial cells and human brain vascular pericytes showed reduced viability, increased caspase-3 activity and enhanced oxidative stress following cisplatin treatment. In addition, cisplatin decreased transendothelial electrical resistance (TEER) and the expression of the tight junction proteins occludin and zonula occludens-1. Curcumin, a polyphenol found in the root of Curcuma longa, had favourable effects on cisplatin neuropathy in previous work. Therefore, curcumin was tested to determine whether it had any effect on these abnormalities. Curcumin alleviated pericyte detachment, cytotoxicity, oxidative stress, TEER reduction and tight junction protein expression. CONCLUSIONS: These data indicate that cisplatin causes BNB disruption in the nerves and might result in neuropathy. Curcumin might improve neuropathy via the restoration of BNB. Whether alterations in the BNB occur and curcumin is effective in patients with cisplatin neuropathy remain to be investigated.

Cisplatin-induced alterations in the blood-nerve barrier: effects of combination of vitamin B1, B6 and B12.

BACKGROUND: Cisplatin is a chemotherapeutic agent against solid cancers. However, neuropathy is a major side effect and has no effective treatment so far. Emerging evidence suggests that cisplatin might damage nerve capillaries leading to impaired blood-nerve barrier (BNB). This study aimed to investigate the ultrastructural changes of the BNB in the sciatic nerves and dorsal root ganglia of rats with cisplatin neuropathy and the effects of B1-6-12. MATERIALS AND METHODS AND RESULTS: The results showed that cisplatin 2 mg/kg injected intraperitoneally twice a week for 5 consecutive weeks caused thermal hypoalgesia and structural abnormalities of nerves and ganglia. Co-treatment with oral B1-6-12 (100:100:1) 100, 300 and 600 mg/kg/day for 5 weeks reduced the sensory deficit and structural alterations. Electron microscopic analysis demonstrated the higher frequencies and wider distances of pericyte detachment in the capillaries of cisplatin than control groups. Vitamin B1, B6 and B12 especially the medium dose, reversed these abnormalities. Culture of endothelial cells and pericytes with cisplatin demonstrated reduced cell viability, increased caspase-3 activity, lower transendothelial electrical resistance and decreased expression of tight junction proteins, occludin and zonula occluden-2. CONCLUSIONS: Vitamin B1, B6 and B12 could correct these toxic effects of cisplatin. These data confirm that cisplatin causes pathological alterations in the components of BNB which correlate with the severity of neuropathy. Furthermore, B1-6-12 is effective against these abnormalities and deserves further investigations as potential treatment for cisplatin-induced neuropathy.

Type and location of flexor hallucis longus musculotendinous junctions and its tendinous interconnections with flexor digitorum longus tendon: pertinent data for tendon harvesting and transfer.

BACKGROUND: Anatomy of flexor hallucis longus (FHL) is essential for the achievement of tendon transfer and several procedures performed in the foot and ankle. The aim of this study was to evaluate the anatomical knowledge of FHL including the type and location of musculotendinous junction (MTJ), tendinous interconnections (TIC) morphology, its location related to Master Knot of Henry (MKH), and the pattern of TIC distribution. MATERIALS AND METHODS: One hundred and sixty-six legs from 52 embalmed and 31 soft cadavers were assessed. The medial (MB) and lateral (LB) bellies of FHL were identified and traced until the end of the most distal muscle fibre to determine the medial and lateral MTJs. MTJ was classified into four types based on the existence and length of MB and LB: type 1, long LB and shorter MB; type 2, equal length of both bellies; type 3, only LB and no MB; type 4, long MB and shorter LB. Low lying muscle belly was defined as muscle extending beyond the zero point (the point of intersection between distal osseous part of tibia and FHL tendon). The distance between MTJ and zero point was measured. TIC was classified into seven types based on the direction and number of slip: type I, one slip from FHL to flexor digitorum longus (FDL); type II, crossed connection: type III, one slip from FDL to FHL; type IV, no connection; type V, two slip from FHL to FDL; type VI, two slip from FHL to FDL and one slip from FDL to FHL; type VII, two slips from FDL to FHL and one slip from FHL to FDL. The distance between the TIC and MKH was measured. TIC distribution was defined into four types based on slip distribution to lesser toes: type a, distributed to second toe; type b, distributed to second and third toes; type c, distributed to second to fourth toes, and type d, distributed to second to fifth toes. RESULTS: Type 1 and type 3 of MTJ morphology were found in 87.3% and 12.7%, respectively. Low lying LB was detected in 66.13% of cases with a mean distance of 13.10 ± 4.51 mm. All MBs ended proximal to the zero point with a mean distance of -21.99 ± 13.21 mm. Three types of TIC (I, II, V) were identified. The highest frequency was type I (82.93%). In addition, a new type of TIC was depicted in 8.53% of cases. Part of the FHL tendon in this type fused with FDL tendon and the rest extended directly to the first toe. TIC could be located either proximal, distal or at the MKH. The highest prevalence was distal to MKH in 51.67% of cases with a mean distance of 11.23 ± 5.13 mm and 8.73 ± 4.2 mm in low lying and non-low-lying groups, respectively. Four types of slip distribution to lesser toes were defined, mostly in type b. No statistically significant differences were detected among all parameters including genders, sides, and groups. CONCLUSIONS: Knowledge of this investigation might enhance the clinical efficacy of tendon harvesting and transfer in foot and ankle surgery.

Evaluation of the greater occipital nerve location regarding its relation to intermastoid and external occipital protuberance to mastoid process lines.

BACKGROUND: Localisation of the greater occipital nerve (GON) is essential for the achievement of several procedures performed in the occipital region especially the treatment of occipital neuralgia. This study proposed to investigate the location of GON subcutaneous (Sc) and semispinalis capitis (SSC) piercing points related to the intermastoid and external occipital protuberance (EOP) to mastoid process (MP) lines. MATERIALS AND METHODS: The Sc piercing point, relation to SSC and obliquus capitis inferior (OCI) muscles of 100 GONs from 50 cadaveric heads (23 males, 27 females) were dissected. Distances from EOP to MP (EM line) on both sides and between MPs (MM line) were measured. Perpendicular lines from Sc and SSC piercing points to EM and MM lines were created and measured. Distances from EOP to the perpendicular lines of SSC piercing point and from MP to the perpendicular lines of Sc piercing point were measured and calculated into percentage of EM and MM length, respectively. RESULTS: Three types of Sc piercing points (I, II and III) were obtained. The percentage of GON piercing trapezius muscle (TP) (type I), aponeurosis of TP (type II) and aponeurosis between TP and sternocleidomastoid muscle (SCM) (type III) were 2, 67 and 31, respectively. In addition, 95% of GON pierced SSC, 2% pierced its tendinous band and 3% travelled between its medial fibres and the nuchal ligament. 94% of the GON turned around the lower edge of the OCI, while 6% pierced the lower edge of this muscle. Sc piercing point was always located above the MM line, but it could be above, below or on the EM line. In contrast, all of the SSC piercing points were located below the EM line except in one specimen, but it could be above, below or on the MM line. Therefore, the MM and EM lines were used as reference lines for locating the Sc and SSC piercing points, respectively. The mean EM line length was 81.26 ± 5.26 mm with statistically significant differences between genders and sides in female. The mean MM line length was 121.77 ± 8.54 mm with a statistically significant difference between genders. Sc piercing point could be located at 44% of MM line length from ipsilateral MP with a mean vertical distance of 18 mm. No statistically significant difference was found between genders and sides in these parameters, but a statistically significant difference was found in the percentage of MB to MM line between type III and type I (p = 0.02). SSC piercing point of all types could be located at the point of 25% of EM line length from EOP with a vertical distance of 18 mm below EM line. No statistically significant difference was found between genders, sides and types of both piercing points. CONCLUSIONS: MM and EM lines are potential reference lines for locating the Sc and SSC piercing points of GON, respectively.

Surface localisation of master knot of Henry, in situ and ex vivo length of flexor hallucis longus tendon: pertinent data for tendon harvesting and transfer.

BACKGROUND: Length of flexor hallucis longus (FHL), localisation of master knot of Henry (MKH) and relationship between MKH and neurovascular bundle are essential for the achievement of FHL tendon transfer. The purpose of this study is to define the localisation of MKH in reference to bony landmarks of the foot, its relationship to plantar neurovascular bundle and to investigate in situ and ex vivo length of FHL tendon in single incision, double incision and minimally invasive techniques. MATERIALS AND METHODS: Foot length was examined in 62 feet of 31 soft cadavers (9 males, 22 females). Various parameters including the relationship between MKH and neurovascular bundle, the distances from MKH to medial malleolus (MM), navicular tuberosity (NT) and the first interphalangeal joint of great toe (IP) were measured. Surface localisation of MKH in relation to a line joining the medial end of plantar flexion crease at the base of great toes (MC) to NT (MC-NT line) was determined. Lengths of FHL tendon graft from three surgical techniques were examined. In situ length was measured in the plantar surface of foot and ex vivo length was measured after tendon was cut from its insertion. RESULTS: The mean length of foot was 230.98 ± 15.35 mm with a statistically significant difference between genders in both sides (p < 0.05). No distance was found between medial plantar neurovascular bundle (MPNVB) and MKH. Mean distance of 17.13 ± 3.55 mm was found between lateral plantar neurovascular bundle (LPNVB) and MKH. MKH was located at a mean distance of 117.11 ± 1.00 mm proximal to IP, 26.28 ± 4.75 mm under NT and 59.58 ± 7.51 mm distal to MM with a statistically significant difference of MKH-IP distance between genders in both sides and MKH-NT in right side. MKH was located anterior to NT (66.1%), at NT (27.4%) and posterior to NT (6.5%) on the MC-NT line. Surface localisation of MKH was 94.75 ± 8.43% of MC-NT line from MC with a perpendicular distance of 25.11 ± 5.37 mm below MC-NT line. The in situ and ex vivo tendon lengths from MTJ to ST, to MKH and to IP were 39.05 ± 10.88 mm and 34.43 ± 10.23 mm, 73.45 ± 9.91 mm and 68.63 ± 9.43 mm, 197.98 ± 13.89 and 191.79 ± 14.00 mm, respectively. A statistically significant difference between genders was found in MTJ-IP of in situ and ex vivo length of both sides (p < 0.05). The mean length of tendon between in situ and ex vivo was significantly different in all techniques (p < 0.05). A moderate positive correlation between foot length and tendon length was found in MTJ-IP of both in situ and ex vivo tendon length. CONCLUSIONS: A statistically significant difference between in situ and ex vivo tendon length was shown in all harvesting techniques. Surface location of MKH was approximately at 95% of MC-NT line from MC with a perpendicular distance of 25 mm from MC-NT line.

Evaluation of the sciatic nerve location regarding its relationship to the piriformis muscle.

BACKGROUND: The localisation of sciatic nerve (SN) is essential for the achievement of several procedures performed in the gluteal region. This study proposed to investigate the location of SN regarding its relationship to the piriformis (PM) by the line joining the posterior superior iliac spine (PSIS), ischial tuberosity (IT) and greater trochanter (GT). MATERIALS AND METHODS: SN-PM relationship was examined in 204 specimens from 102 embalmed cadavers (55 males, 47 females). Distances between PSIS, IT and GT were measured. Midpoints of SN at the lower edge of PM (S1) and IT-GT line (S2) were marked. Perpendicular line from S1 to PSIS-GT (S1-R) and to PSIS-IT (S1-Q), were created and measured. Distances of PSIS-R, PSIS-Q (S1) and IT-S2 were measured and calculated into percentage of PSIS-GT, PSIS-IT and IT-GT lengths, respectively. RESULTS: Regarding the classification of Beaton and Anson, three types of SN-PM relationship (a, b and c) were obtained. The percentage of type a, b and c was 74.02, 22.55 and 3.43, respectively. Symmetrical SN-PM relationship was found in 75.49%. The mean length of PSIS-IT, PSIS-GT and IT-GT in all types was 129.63 ± 11.89 mm, 151.34 ± 14.78 mm and 73.02 ± 10.20 mm, respectively. A statistically significant difference was found between types a and b (p = 0.013) in PSIS-IT length, whereas mean length of IT-GT and PSIS-GT showed no statistically significant difference between SN-PM types. PSIS-IT line passed SN at the lower edge of PM (S1) in 112 specimens (54.90%). In these cases, S1 and Q were the same point. A statistically significant difference was also found between types a and b (p = 0.023) in PSIS-Q (S1) length. The mean lengths of PSIS-Q (S1), PSIS-R and IT-S2 in term of percentage of PSIS-IT, PSIS-GT and IT-GT line in all types were 60.06 ± 5.90%, 54.19 ± 6.10%, and 37.87 ± 8.27%, respectively. The mean lengths of S1-R and S1-Q were 30.07 ± 8.30 mm and 6.54 ± 7.99 mm. Therefore, SN at S1 could be located at the point of 54.19 ± 6.10% of PSIS-GT length (R) with a distance of 30.07 ± 8.30 mm perpendicular to PSIS-GT line (S1-R). Since the PSIS-IT line did not pass SN at S1 in every case, it might not be suitable for localizing SN at S1. SN at S2 could be located at the point of 37.87 ± 8.27% of IT-GT line. No significant difference was found between types. CONCLUSIONS: Sciatic nerve can be localised by PSIS-GT and IT-GT lines without statistically significant difference between types (a, b, and c) of SN-PM relationship.

Morphometric study of inferior peroneal retinaculum and contents of inferior peroneal tunnel.

BACKGROUND: The aims of this study are to investigate the inferior peroneal retinaculum (IPR) regarding morphometric parameters, and contents in the inferior peroneal tunnel (IPT). MATERIALS AND METHODS: One hundred and nine embalmed cadaveric legs were dissected in prone position. RESULTS: The extension band of the IPR was found in 31.19% of cases. The mean of length, width at the origin, width at the middle part, width at the insertion, and thickness of the IPR [mm] were 23.42 ± 3.54 (17.05-33.68), 13.29 ± 2.56 (5.83-20.92), 14.50 ± 2.37 (6.68-21.34), 10.10 ± 2.63 (4.59-19.17) and 0.48 ± 0.16 (0.20-0.87), respectively. The angle of the IPR to the horizontal axis was 38.51 ± 7.07 (11.67-54.00) degrees. The IPT was divided into the upper and lower tunnels. The normal contents were the tendons of peroneus brevis and peroneus longus in the upper and lower tunnels, respectively. However, additional contents were found in the upper tunnel in 2 cases. One was the tendon of peroneus digiti quinti, and peroneus quartus in the other one. Moreover, an unusual accessory peroneal muscle coursed into the lower tunnel and inserted on the peroneal tubercle. Tears of the peroneus brevis tendon were observed in 2 cases. CONCLUSIONS: These morphometric data might be beneficial in surgical repair for IPR injury.

Activation of MAPK ERK in peripheral nerve after injury.

BACKGROUND: Activation of extracellular signal-regulated protein kinase (ERK), a member of mitogen-activated protein kinase (MAPK) family, has been proposed to mediate neurite outgrowth-promoting effects of several neurotrophic factors in vitro. However, the precise activity of ERK during axonal regeneration in vivo remains unclear. Peripheral axotomy has been shown to activate ERK in the cell bodies of primary afferent neurons and associated satellite cells. Nevertheless, whether ERK is also activated in the axons and surrounded Schwann cells which also play a key role in the regeneration process has not been clarified. RESULTS: Phosphorylation of ERK in the sciatic nerve in several time-points after crush injury has been examined. Higher phosphorylation of ERK was observed in the proximal and distal nerve stumps compared to the contralateral intact nerve from one day to one month after crush. The activation of ERK was mainly localized in the axons of the proximal segments. In the distal segments, however, active ERK was predominantly found in Schwann cells forming Bungner's bands. CONCLUSION: The findings indicate that ERK is activated in both the proximal and distal nerve stumps following nerve injury. The role of activated ERK in Wallerian degeneration and subsequent regeneration in vivo remains to be elucidated.

Morphometric data of normal sural nerve in Thai adults.

Morphometry has an important role in the interpretation of sural nerve biopsies. It is used for early detection of structural abnormalities in peripheral neuropathies. This application requires a comparison with data of normal population. However, most data in the literature were of Western subjects with a small number of samples. In this study the authors reported the morphometric data of sural nerve harvested within 24 hours after death from 78 Thai subjects without known causes of neuropathy. The samples were transversely sectioned and analyzed for the number and area of fascicles, the total number of myelinated axons, myelinated fiber diameter; myelinated axon diameter, myelin sheath thickness, g ratio and myelinated axon density. Results were discordant in some measurement parameters compared to previous reports. These data are valuable for the early recognition of peripheral nerve diseases from biopsied sural nerve of Thai subjects.

A role for mitogen-activated protein kinases in the etiology of diabetic neuropathy.

The onset of diabetic neuropathy, a complication of diabetes mellitus, has been linked to poor glycemic control. We tested the hypothesis that the mitogen-activated protein kinases (MAPK) form transducers for the damaging effects of high glucose. In cultures of adult rat sensory neurons, high glucose activated JNK and p38 MAPK but did not result in cell damage. However, oxidative stress activated ERK and p38 MAPKs and resulted in cellular damage. In the dorsal root ganglia of streptozotocin-induced diabetic rats (a model of type I diabetes), ERK and p38 were activated at 8 wk duration, followed by activation of JNK at 12 wk duration. We report activation of JNK and increases in total levels of p38 and JNK in sural nerve of type I and II diabetic patients. These data implicate MAPKs in the etiology of diabetic neuropathy both via direct effects of glucose and via glucose-induced oxidative stress.

New classification of histochemical staining patterns of acetylcholinesterase activity in rectal suction biopsy in Hirschsprung's disease.

Several previous studies have introduced classifications of Acetylcholinesterase (AChE) histochemical staining patterns in rectal suction biopsy performed in patients with Hirschsprung's disease. However, we introduce a new classification that is less complicated but shows the same age dependence as seen in previous studies. 135 rectal suction biopsies were submitted to histochemical staining for AChE activity and 88 specimens showed increased AChE activity. Therefore, we retrospectively analysed these 88 cases and could establish three patterns. Pattern I, presence of thick nerve trunks or coarse nerve fibers only in the muscularis mucosae and submucosa. This pattern was mainly seen in children aged 6 months or below. Pattern II, presence of abundant nerve fibers in all three layers of mucosa. This pattern was predominantly seen in children over 6 months of age. Pattern III, not predominant in any age group, showed positive nerve fibers in all three layers but, in one or more layers, the nerve fibers were sparse. Upon comparison with previous studies, we could observe the same age-pattern relationship. Thus, we propose this method of classification as a new tool to classify AChE histochemical staining patterns.

Inhibition of MAPK ERK impairs axonal regeneration without an effect on neuronal loss after nerve injury.

UNLABELLED: Activation of extracellular signal-regulated protein kinase (ERK), a member of the mitogen-activated protein kinase family, has been shown to mediate neurite outgrowth-promoting effects of various neurotrophic factors in vitro. Moreover, in vivo, ERK is activated in the primary sensory neurons and associated glial cells after nerve injury. However, the precise role of ERK in nerve regeneration remains unclear. OBJECTIVE: This work was aimed to investigate the effects of ERK inhibition on axonal regeneration and neuronal loss after axotomy. METHODS: Unilateral sciatic nerve crush was performed, and inhibition of ERK was achieved by intraperitoneal injection of 300 microg kg(-1) day(-1) of u0126 for 2 weeks in the inhibitor group. For the control group, only the vehicle was given with the same schedule. RESULTS: ERK was activated in the crushed sciatic nerve, and this was significantly reduced by the inhibitor. In contrast, there was no activation of ERK in the L4/L5 spinal ganglia. Morphological analysis revealed the similar extent of neuronal loss in the two groups. In addition, the mean regeneration distance in the inhibitor group was lower than that of the control group. CONCLUSION: These results suggest the crucial role of ERK in nerve regeneration but not sensory neuronal loss after trauma.

Phosphorylation of c-Jun N-terminal kinase (JNK) in sensory neurones of diabetic rats, with possible effects on nerve conduction and neuropathic pain: prevention with an aldose reductase inhibitor.

AIMS/HYPOTHESIS: This study was designed to determine whether diabetes in rats is associated with phosphorylation of c-Jun N-terminal kinase (JNK) and one of its transcription factors, c-Jun, in sensory neurones innervating the lower limb. We also sought to determine which neuronal phenotypes are affected and to examine the effect of aldose reductase inhibition on JNK and c-Jun phosphorylation. METHODS: Diabetes was induced in rats using streptozotocin. Phosphorylation of JNK and c-Jun in lumbar dorsal root ganglia was determined by binding of phospho-specific antibodies using western blots and immunocytochemistry. Neuronal phenotypes were characterised by binding of N52 (an antibody that recognises the heavy neurofilament protein; for large-diameter mechanoceptors) and of calcitonin gene-related peptide and the plant glycoprotein lectin IB4 (for nociceptors). The efficacy of the aldose reductase inhibitor fidarestat was determined by measuring polyol pathway metabolites in sciatic nerve, and functionally by measuring the conduction velocity of motor and sensory nerves. RESULTS: In control rats, activated JNK and c-Jun were primarily associated with mechanoceptors; in diabetes this was increased, but a greater increase was seen in nociceptors. Phosphorylation was prevented in all cells by fidarestat, which normalised polyol pathway metabolites as well as motor nerve and sensory nerve conduction velocity. CONCLUSIONS/INTERPRETATION: Fidarestat-sensitive phosphorylation of JNK and c-Jun occurs in fast-conduction mechanoceptors-the same class of neurones that registers the changes in sensory nerve conduction velocity-and in nociceptors. This supports the notion that mitogen-activated protein kinase phosphorylation, via the polyol pathway, may convert the direct effects of raised glucose into impaired nerve conduction and neuropathic pain. For proof of this we await the availability of specific JNK antagonists formulated for in vivo use.