Introduction: Low back pain (LBP) is often reported as dull pain in the deep, musculoskeletal system around the lumbar spine. Although the chronic LBP could potentially involve the supraspinal pathology, its cerebral substrates have not been defined. We have developed a human model of LBP to identify such substrates by functional magnetic resonance imaging (fMRI) and further to investigate the plastic changes that may underlie the chronic progression of LBP.
   Methods: Six healthy volunteers, laid in the prone position in a 3-Tesla MRI scanner, were stimulated with a tail of an occluded disposable 20-ml syringe, filled with 25-ml air, orthogonally placed at 5 cm lateral to the L4/5. Calibrated, manual pressure was applied on the syringe so that each subject reported pain intensity at either 3 or 5 out of 10-cm visual analogue scale (VAS). Three blocks of 30-s pain stimulus, at either 3 or 5 of VAS, were given with 30-s intervening rest conditions, while the whole-brain gradient-echo echo-planar imaging, optimized for blood oxygenation level-dependent (BOLD) contrast, was performed. Functional data were aligned with each subject's 3-dimentional high-resolution image obtained during the same session, and analyzed with general linear model using BrainVoyager QX (BrainInnovation, Maastricht, Netherlands). After being averaged across subjects, the cerebral activation map was obtained with the false discovery rate at q<0.05.
   Results: The average force required to induce pain at the VAS of 3 and 5 was 376 ± 72 kPa and 538 ± 66 kPa, respectively. Pain at the VAS of 3 and 5 commonly activated the prefrontal cortex and the supplementary motor area at nearly the same BOLD amplitude, but spared the primary and secondary somatosensory cortices.
   Discussion: The present model of LBP induced cerebral activation in the medial nociceptive system and the motor-related areas, but did not show any activation in the lateral nociceptive system. Such lack of somatotopic representation might indicate that the present model of LBP involves the deep, heterogeneous structures around the lumbar spine.

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   We have been carrying out basic studies employing rats to clarify the segmental structure of the peripheral nerves, thereby establishing a rat map. In this paper, we present a potential human map of the segmental structure of the sensory nerves that was determined from the rat map and discuss pain sensation areas in lumbar radiculopathy. The somatic tissues innervated by sensory fibers involved in a spinal nerve, provisionally termed as "sensoritomes",could be considered as the space (or surface) extending between the rami of the spinal nerve. Sensoritomes are shaped like a "deformed cone" due to the caudal inclination of spinal nerve rami. The boundary lines of sensoritomes crossed the lumbar spine obliquely. The lines ran cranio-dorsally to caudo-ventrally in the lateral side of the coxal bone, converging toward the pubis symphysis. The boundary surfaces of sensoritomes in the hindlimb were formed by the lateral expansion of the boundary lines in the coxal bone. Pain sensation areas in lumbar radiculopathy, which were identical to sensoritomes, were predicted as follows. L4: ilium - hip joint - femur-knee joint - medial tibia - first digit. L5: Dorsal surface of ilium - gluteus medius muscles - hamstrings - tibia-medial foot. S1: ischii - gluteus maximus - hamstrings - fibula - lateral foot. The sensoritome of S1 was located more caudally and dorsally in the body trunk, more dorsally in the thigh, and more laterally in the leg and foot than that of L5. It was suggested that L5 and S1 radiculopathies could be discriminated and therefore diagnosed by referring pain distribution to the human sensoritome map.

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   TRPA1 and TRPV1, members of the TRP family, are Ca²⁺-permeable cation channels and expressed in small-diameter dorsal root ganglion neurons. TRPA1 is activated by noxious cold (< 17°C), mechanical stimulation, and pungent ingredients such as cinnamaldehyde (CA) and allyl isothiocyanate. TRPV1 is opened by noxious heat (> 43°C), low pH and capsaicin (CAP). Recent studies have shown that TRPA1 and TRPV1 act on presynaptic terminals in the substantia gelatinosa (SG, lamina II of the spinal dorsal horn) to enhance the glutamate release. However, it is not fully understood how nociceptive transmission is finally modified by the activation of spinal TRPA1 and TRPV1. In this study, we investigated the effects of CA and CAP on spontaneous excitatory postsynaptic currents (EPSCs) evoked in SG neurons of adult rat spinal cord slices by using the whole-cell patch-clamp technique. Under voltage-clamp conditions, CA (300 µM) increased the frequency and amplitude of spontaneous EPSCs while it increased only the frequency of miniature EPSCs elicited in the presence of tetrodotoxin (1 µM). The excitatory effect of CA on spontaneous EPSCs was observed in about 30% of total neurons tested. In morphological analysis, the SG neurons sensitive to CA were identified as the vertical neuron. CAP (1 µM) also increased the frequency of spontaneous EPSCs in most of the SG neurons recorded. In all of the SG neurons sensitive to CA, CAP also increased the frequency of sEPSCs. On the other hand, CA and CAP had no effects on the frequency and amplitude of GABAergic and glycinergic spontaneous IPSCs. These results suggest that CA and CAP act on TRPA1 and TRPV1 receptors expressed in the presynaptic terminals of C fibers to facilitate miniature release of glutamate, and CA more selectively acts on excitatory neurons in the SG. These actions may contribute to spinal modulation of nociceptive transmission.

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   Sensitization in the spinal dorsal horn is believed to be a cellular mechanism for enhanced pain sensitivity. In this study, by using optical imaging with voltage-sensitive dye, we measured the neuronal excitation in spinal cord slices from normal rats and Complete Freund's Adjuvant (CFA)-induced arthritis rats. The amplitude of evoked-neuronal excitation in the substantia gelatinosa of arthritis rats was larger than normal rats and inhibited in the presence of a glial TCA cycle inhibitor, monofluoro-acetic acid. A gap-junction blocker, carbenoxolone inhibited neuronal excitation in arthritis rats one hour, but not one day after injection of CFA. In contrast, a microglial inhibitor minocycline, as well as P2Y receptor antagonsist reactive blue,inhibited neuronal excitation in arthritis rats one day, but not one hour after injection. These results suggest that facilitation of neuronal excitation mediated by glial cells in the gelatinosa underlies the induction of mechanical hyperalgesia in arthritis rats, and that the functional changes in glial cells take place in early stage of the arthritis.

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   Background: Sweet substance-induced analgesia (SIA) has been widely investigated in rodents. The mechanism is thought to be involved in the central regulating systems in the anti-nociceptive process, taking advantage of sweet taste and not acting as a distraction. In human, this SIA is, however, limited in neonatal. The reasons underlying the reduced effects of SIA with growth have been less studied in adults. Consensus regarding SIA thus has not yet to be obtained in adults. Therefore, we aimed to determine the sweet stimulus of sucrose on responses of healthy adults to nociception using cold pressor testing.
   Methods: The present study was carried out a randomized control with crossover design. Using the cold pressor test (CPT), 13 adult male subjects immersed a hand in cold water to induce nociception. Subjects held either a 24% weight ⁄ volume sucrose solution or distilled water in their mouth before and during CPT. Analgesic effect and emotional state were quantitatively assessed as follows: pain threshold; pain tolerance; pain intensity; taste pleasantness; and the brief Japanese version of the Profile of Mood State (POMS).
   Results: With subjects held sucrose solution in the mouth, pain threshold was increased significantly (p<0.05) when compared with distilled water. In addition, the taste pleasantness rating was significantly higher with sucrose solution than that with distilled water (p<0.05).
   Conclusions: These data clearly indicate that the sweet stimulus of sucrose induces anti-nociception associated with taste pleasantness in adults, suggesting sweet substance-induced analgesia can be applied to young male adults.

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