Opioids induce postural asymmetry in spinal rat: the side of the flexed limb depends upon the type of opioid agonist

Abstract

The κ-agonists bremazocine and dynorphin (1–13), the σ-agonist SKF 10.047 as well as the σ-agonists [ d-Ala 2, [ d-Ala 2, d-Leu 5]-enkephalin (DADL) and Met-enkephalin, but not the μ-agonist morphine, applied subarachnoidally to the could portion of the transected spinal cord (at the T 3-T 4 level) induced postural asymmetry of the hind limbs in rats. Asymmetry was registered visually. The leg was regarded as flexed if its projection on the longitudinal axis of the animal was smaller than that on its counterpart. The side of the flexed leg depended upon the type of drug: bremazocine, dynorphin(1–13) and Met-enkephalin predominantly induced flexion of the right leg, SKF 10.047 induced flexion of the left leg (at some doses there is no side preference), while in the case of DADL the side of the flexed leg depended upon the dose of the drug. Comparison of electromyographic activity of the symmetric biceps and quadriceps femoris revealed that bremazocine considerably facilitates the flexion reflex of the right hind limb without affecting the left limb reflex. As a rule, a flexed leg determined visually exhibited higher EMG activity of the biceps femoris as compared with a symmetric one. The opiate antagonist naloxone significantly reduced the percentage of animals with postural asymmetry. The magnitude of asymmetry and the side of flexion were not constant in some animals, but changed with time. However, the mean magnitude of asymmetry, the percentage of animals with asymmetry and the left/right flexion ratio in each group of animals remained constant. The side of flexion also depended upon the level of spinal cord transection: bremazocine and Met-enkephalin injected subarachnoidally following transection at the T 1-T 4 and T 5-T 6 levels predominantly induced flexion of the right and the left leg, respectively. Asymmetry did not develop in physiologically intact animals given bremazocine, even if the spinal cord was cut later, i.e. transection of the spinal cord was necessary for the development of asymmetry. These data indicate that the neurons which maintain muscular tone of the hind limbs and which are located symmetrically to the sagittal plane, have different sensitivities to κ-, σ-, and σ-agonists. In most animals, neurons with a higher specificity to some agonist are localized on one side of the sagittal plane.