Korean J Physiol Pharmacol.  2008 Oct;12(5):253-258. 10.4196/kjpp.2008.12.5.253.

Effects of Somatostatin on the Responses of Rostrally Projecting Spinal Dorsal Horn Neurons to Noxious Stimuli in Cats

Affiliations
  • 1Department of Physiology, Kangwon National University College of Medicine, Chunchon, Korea. eurijj@naver.com
  • 2Department of Orthopedics, Kangwon National University College of Medicine, Chunchon, Korea.
  • 3Department of Physiology, School of Dentistry and Dental Research Institute, Seoul National University, Seoul, Korea.

Abstract

Somatostatin (SOM) is a widely distributed peptide in the central nervous system and exerts a variety of hormonal and neural actions. Although SOM is assumed to play an important role in spinal nociceptive processing, its exact function remains unclear. In fact, earlier pharmacological studies have provided results that support either a facilitatory or inhibitory role for SOM in nociception. In the current study, the effects of SOM were investigated using anesthetized cats. Specifically, the responses of rostrally projecting spinal dorsal horn neurons (RPSDH neurons) to different kinds of noxious stimuli (i.e., heat, mechanical and cold stimuli) and to the A delta-and C-fiber activation of the sciatic nerve were studied. Iontophoretically applied SOM suppressed the responses of RPSDH neurons to noxious heat and mechanical stimuli as well as to C-fiber activation. Conversely, it enhanced these responses to noxious cold stimulus and A delta-fiber activation. In addition, SOM suppressed glutamate-evoked activities of RPSDH neurons. The effects of SOM were blocked by the SOM receptor antagonist cyclo-SOM. These findings suggest that SOM has a dual effect on the activities of RPSDH neurons; that is, facilitation and inhibition, depending on the modality of pain signaled through them and its action site.

Keyword

Somatostain; Spinal cord; Dorsal horn; Nociception; A delta-fiber; C-fiber; Pain

MeSH Terms

Animals
Cats
Central Nervous System
Cold Temperature
Hot Temperature
Neurons
Nociception
Posterior Horn Cells
Sciatic Nerve
Somatostatin
Spinal Cord
Somatostatin

Figure

  • Fig. 1. Effects of iontophoretically applied SOM on the RPSDH neuron response to peripheral noxious stimuli. Single cell activity was recorded in the lumbosacral area using an extracellular electrode. (A) RPSDH neurons exhibit several characteristics; namely, 1) constant latency, 2) the responses to high frequency (333 Hz) stimulation, and 3) collision. Arrow (↑) represents the electrical stimuli to sciatic nerve. The activity of RPSDH neuron (•) by electrical stimuli was observed after a constant latency. Gray circle (•) means the activity of RPSDH neuron, which vanished after collision (▼) by cervical dorsal column stimulation. In this experiment, RPSDH neurons were used. (B) Iontophoretic application of SOM (100 nA) resulted in the inhibition of nociceptive response to noxious heat (50°C) stimuli subjected for a 20 sec duration and to mechanical stimuli (squeeze) for 10 sec. After an iontophoretic application of SOM (100 nA), the heat-evoked and the noxious mechanically evoked responses were suppressed. (C) The effects of SOM on the response of RPSDH neuron to peripheral noxious cold stimulation are presented. SOM (100 nA) increased the cold-evoked response of the RPSDH neuron. Each bar graph represents mean value±standard error for SOM effect on noxious stimuli such as heat, squeeze, and cold. The asterisk shows significant difference in SOM effect (non paired t-test, p<0.05).

  • Fig. 2. Effects of iontophoretically applied SOM on the RPSDH neuron response to noxious electrical stimuli of the peripheral nerve. (A) The single (↑) or triple (↑ ↑↑) electrical stimulation at 500 ms was applied to the sciatic nerve with Aδ-strength (1 mA with 0.1 ms width) or with C-strength (10 mA with 0.5 ms width). SOM increased Aδ -fiber response of this cell, whereas the C-fiber response of the same cell was markedly suppressed. The summary bar graph was derived from the normalized SOM effect on Aδ- (Aδ-R) and C-responses (C-R). (B) Electrical stimuli were applied to the sciatic nerve for the activation of Aδ-or C-fibers (a single or a train of three square wave pulses). In doing so, the responses were discriminated using window discriminator. The Aδ -response was the sum of activities appearing in less than 50 ms, while the C-response are those after 150 ms. Evoked responses were expressed as the total number of impulses. Also, twenty sweeps were compiled as a peristimulus time histogram (bin width; 2 ms, 20 sweeps). The bar graph represents mean value±standard error for SOM effect on noxious electrical stimuli. The significant difference in SOM effect (non paired t-test, p<0.05) is represented by the asterisk.

  • Fig. 3. Blockade of SOM effect by SOM receptor antagonist, cyclo-SOM. The cyclo-SOM (100 nA) blocked the inhibitory effects of SOM (100 nA) on heat (59.2±9.8→80.8±11.5%, n=5) and squeeze (74.6±4.6→90.3±6.9%, n=6) as well as the facilitatory effect on cold stimulation (151.5±11.5→110.8±6.6%, n=4). In the case of activities by electrical stimuli such as Aδ – and C-response, SOM effect was also inhibited by cyclo-SOM (Aδ-response, 135.4±6.2→105.4±9.2%, n=5; C-response, 64.6±7.7→93.8±5.2%, n=5). Each bar graph represents mean value±standard error for SOM-and cyclo-SOM effect on noxious stimuli. The asterisk shows significant difference in SOM effect (paired t-test, p<0.05).

  • Fig. 4. Effects of SOM on glutamate-evoked activity of RPSDH neuron. Iontophoretical application of GLU (100 nA every 5 seconds) induced the activity of RPSDH neuron. SOM has inhibitory action on the GLU-evoked activity of RPSDH neuron in a dose dependent manner (SOM1, 100 nA; SOM2, 200 nA). This inhibitory effect of SOM was blocked by cyclo-SOM (100 nA). Each bar graph represents mean value±standard error for SOM- and cyclo-SOM effect on glutamate-evoked activity of RPSDH neuron. Similarly, the asterisk shows significant difference in SOM effect (paired t-test, p<0.05).


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