The central nervous system (CNS) is involved in a variety of disease conditions. Some seeming peripheral diseases, like chronic pain and disorders in major organs, indeed have clear pathological basis in the CNS. On the other hand, some clinically-beneficial peripheral stimulation, such as acupuncture and massage, exerts significant influence on central neurons. This review attempts to summary recent findings in neuroscience about how pathological insults long-term plastic changes within neural circuits, leading to maladaptive behaviors. This neuroplasticity-based theory not only conceptualizes a cellular mechanism for a plethora of neuropathophysiology but also provides clinical strategies for treating neural diseases. Drug addiction is a chronic brain disease, defined as compulsive drug-seeking, drug-craving, and drug-taking behaviors. Extensive experimental evidence suggests that following exposure to drugs of abuse, neurons within the mesolimbic dopamine system undergo a series of plastic changes that may lead to compulsive emotional and motivational states. It is believed that the first step to unlock the secret of drug addiction is to identify, evaluate, and conceptualize drug-induced neural plasticity. Synaptic plasticity is one form of neuroplasticity that has been best characterized. Using addiction-related synaptic plasticity as a working model, this review attempts to depict the general concept and experimental approach in studying the pathophysiological neural basis of acupuncture.