Regulation of opioid binding sites in the superficial dorsal horn of the rat spinal cord following loose ligation of the sciatic nerve: Comparison with sciatic nerve section and lumbar dorsal rhizotomy

The aim of the present study was to quantify time-related modifications in μ and δ opioid binding sites in the superficial layers (laminae I and II) of the L4 lumbar segment in a rat model of mononeuropathy induced by loose ligation of the sciatic nerve. We have shown a 28% (P < 0.01) and 24% (P < 0.01) decrease in ipsi/contralateral side binding ratios for tritiated (Tyr*-d-Ala-Gly-NMe-Phe-Gly-ol) ([3H]DAMGO) and tritiated (Tyr*-d-Thr-Gly-Phe-Leu-Thr) ([3H]DTLET) respectively, at two weeks postlesion which correspond to the delay of maximal hyperalgesia and of maximal alteration of fine diameter primary afferent fibers. In contrast, no change in [3H]U.69593 specific binding could be detected at this postlesion delay. For longer survival delays (four, eight and 15 weeks postlesion), μ and δ binding ratios return towards control values (approximately equal to 1), probably reflecting the occurrence of a long-term neuroplasticity (i.e. a new equilibrium in the metabolism of primary neurons, or collateral sprouting from intact primary afferents) following loose nerve ligation. In addition, a comparison of the results obtained in this model with those measured after sciatic nerve section and lumbar dorsal rhizotomy was performed in order to compare the degree of loss in opioid binding sites in these three types of lesion. The section of the sciatic nerve induced at eight days postlesion an 18% (P < 0.01) and 28% (P < 0.01) decrease in binding ratio for [3H]DAMGO and [3H]DTLET, respectively. At two weeks postlesion the loss was 24% (P < 0.01) for the two ligands, and at longer delays (four and 12 weeks), a progressive recovery in binding ratio was observed. Thus, it appears that both sciatic nerve lesions we have studied result in μ and δ binding modifications which have similar intensity and similar time course from two to 12–15 weeks postlesion. In contrast, the unilateral rhizotomy of nine consecutive dorsal roots (T13-S2), which is known to induce a massive degeneration of fine diameter primary afferent fibers, is followed by a dramatic decrease in binding ratios for [3H]DAMGO (53%, P < 0.001) and [3H]DTLET (45%, P < 0.001) at two weeks postlesion. These data suggest that the more deprived the dorsal horn is of fine diameter primary afferent fibers, the more dramatic is the opioid binding loss in the ipsilateral side as compared to the contralateral side. However, when considering specific binding concentration, it must be emphasized that regulation can occur independently of a direct alteration of primary afferent fibers. A significant up-regulation in μ binding sites was found at every postlesion delay following nerve loose ligation and only at eight days following nerve section. This up-regulation seems to be bilateral although, on the ipsilateral side, this effect could be masked by the fiber degeneration. We propose that this up-regulation in μ binding sites could result from the activation of endogenous opioid control systems due to the alteration of nociceptive sensory input. Our results are discussed in view of the recent controversy arising on the efficacy of opiates in neuropathic pains.