Abstract:
The intervertebral disc is avascular. With aging, calcified layers occlude the capillaries at the cartilaginous endplates, reducing diffusion of nutrients and oxygen from capillaries into the avascular disc. Under anaerobic condition, excessive production of lactic acid decreases intradiscal pH and irritates surrounding nerves, causing persistent back pain. Antacid is injected into the painful disc to increase pH and alleviate back pain.

Description:
FIELD OF INVENTION 
     This invention relates to methods for increasing pH within an intervertebral disc by injecting antacid to neutralize lactic acid, thereby reducing acid irritation and back pain. 
     BACKGROUND 
     Low back pain is a leading cause of disability and lost productivity. Up to 90% of adults experience back pain at some time during their lives. Back pain is second only to upper respiratory infections in frequency of physician visits. In the United States, the economic impact of this malady has been reported to range from $50-$100 billion each year, disabling 5.2 million people. Though the sources of low back pain are varied, the intervertebral disc is thought to play a central role in most cases. Degeneration of the disc initiates pain in other tissues by altering spinal mechanics and producing non-physiologic stress in surrounding tissues. 
     A healthy intervertebral disc absorbs most of the compressive load of the spine. The facet joints  129  of the vertebral bodies  159  share only about 16% of the load. The disc  100  consists of three distinct parts: the nucleus pulposus  128 , the annular layers  378  and the cartilaginous endplates  105 , as shown in  FIG. 1 . The disc maintains its structural properties largely through its ability to attract and retain water. A normal disc  100  contains 80% water in the nucleus pulposus  128 . The nucleus pulposus  128  within a normal disc  100  is rich in water absorbing sulfated glycosaminoglycans, creating the swelling pressure to provide tensile stress within the collagen fibers of the annulus  378 , as shown in  FIG. 2 . The swelling pressure produced by high water content is crucial to supporting the annular layers  378  for sustaining compressive loads. 
     In adults, the intervertebral disc is avascular. Survival of the disc cells depends on diffusion of nutrients from blood vessels  112  and capillaries  107  within the vertebral bodies  159  through the cartilage  106  of the endplates  105 , as shown in  FIG. 2 . Diffusion of nutrients also permeates from peripheral blood vessels adjacent to the outer annulus  378 , but these nutrients can only permeate up to 1 cm into the annular layers  378  of the disc. An adult disc can be as large as 5 cm in diameter; hence diffusion through the cranial and caudal endplates  105  is crucial for maintaining the health of the nucleus pulposus  128  and inner annular layers  378  of the disc  100 . 
     Calcium pyrophosphate and hydroxyapatite are commonly found in the endplate  105  and nucleus pulpous  128 . Beginning as young as 18 years of age, calcified layers begin to accumulate in the cartilaginous endplate  105 . The blood vessels  112  and capillaries  107  at the bone-cartilage  106  interface gradually occlude due to the build-up of calcified layers  108  which form into bone, as shown in  FIG. 3 . Bone formation at the endplate  105  increases with age. 
     When the endplate  105  is obliterated by bone, diffusion of nutrients and oxygen through the calcified  108  endplate  105  into the avascular disc  100  is greatly diminished. Oxygen concentration in the central part of the nucleus is extremely low. Cellularity of the disc is already low compared to most tissues. To obtain necessary nutrients and oxygen, cell activity is restricted to being at or in very close proximity to the cartilaginous endplate  105 . Furthermore, oxygen concentrations are very sensitive to changes in cell density or consumption rate per cell. 
     The supply of sulfate into the nucleus pulposus  128  for biosynthesizing sulfated glycosaminoglycans is also restricted by the calcified  108  endplates  105 . As a result, the sulfated glycosaminoglycan concentration decreases, leading to lower water content and swelling pressure within the nucleus pulposus  128 . During normal daily compressive loading on the spine, the reduced pressure within the nucleus pulposus  128  can no longer distribute the forces evenly along the circumference of the inner annulus  378  to keep the lamellae bulging outward. As a result, the inner lamellae sag inward, while the outer annulus  378  continues to bulge outward, causing delamination  114  of the annular layers  378 , as shown in  FIG. 3 . 
     The shear stresses causing annular delamination  114  and bulging are highest at the posteriolateral portions adjacent to the neuroforamen  121 . The nerve  194  is confined within the neuroforamen  121  between the disc and the facet joint  129 . Hence, the nerve  194  at the neuroforamen is vulnerable to impingement by the bulging disc  100  or bone spurs, as shown in  FIG. 4 . 
     When oxygen concentration in the disc falls below 0.25 kPa (1.9 mm Hg), production of lactic acid dramatically increases with increasing distance from the endplate. The pH within the disc falls as lactic acid concentration increases. Lactic acid diffuses through micro-tears of the annulus irritating the richly innervated posterior longitudinal ligament  195 , facet joint  129  and/or nerve root  194 ,  FIG. 4 . Studies indicate that lumbar pain correlates well with high lactate levels and low pH (Diamant B., Karlsson J., Nachemson A.: Correlation between lactate levels and pH in discs of patients with lumbar rhizopathies, Experientia, Dec 15:24(12), 1195-1196, 1968). The mean pH of symptomatic discs was significantly lower than the mean pH of the normal discs (Kitano T., Zerwekh J E, Usui Y., Edwards M L, Flicker P L, Mooney V.: Biochemical changes associated with the symptomatic human intervertebral disk, Clinical Orthopedic Related Research, August (293), 372-377, 1993). The acid concentration is three times higher in symptomatic discs than normal discs. In symptomatic discs with pH 6.65, the acid concentration within the disc is 5.6 times the plasma level. In some preoperative symptomatic discs, nerve roots were found to be surrounded by dense fibrous scars and adhesions with remarkably low pH 5.7-6.30 (Nachemson A: Intradiscal measurements of pH in patients with lumbar rhizopathies, Acta Orthop. Scand. 40(1), 23-42, 1969). The acid concentration within the disc was as high as 50 times the plasma level. 
     Approximately 85% of patients with low back pain cannot be given a precise pathoanatomical diagnosis. Many of these patients are generally classified having “non-specific pain”. Back pain and sciatica can be recapitulated by maneuvers that do not affect the nerve root, such as intradiscal saline injection, discography, and compression of the posterior longitudinal ligaments. It is possible that some non-specific pain is caused by lactic acid irritation secreted from the disc. Injection into the disc can flush out the lactic acid. Maneuvering and compression can also drive out the irritating acid to produce non-specific pain. Currently, no intervention other than discectomy can halt the production of lactic acid. 
     The nucleus pulposus is thought to function as “the air in a tire” to pressurize the disc. To support the load, the pressure effectively distributes the forces evenly along the circumference of the inner annulus  378  and keeps the lamellae bulging outward. The process of disc  100  degeneration begins with calcification  108  of the endplates  105 , which hinders diffusion of sulfate and oxygen into the nucleus pulposus  128 . As a result, production of the water absorbing sulfated glycosaminoglycans is significantly reduced, and the water content within the nucleus decreases. The inner annular lamellae  378  begin to sag inward, and the tension on collagen fibers within the annulus  378  is lost, as shown in  FIG. 3 . The degenerated disc exhibits unstable movement, similar to a flat tire. Approximately 20-30% of low-back-pain patients have been diagnosed as having spinal segmental instability. The pain may originate from stress and increased load on the facet joints  129  and/or surrounding ligaments. 
     Sulfate is an essential ingredient for biosynthesizing the sulfated glycosaminoglycans responsible for retaining water within the intervertebral disc  100 . The rate of sulfate incorporation into the disc  100  is pH sensitive (Ohshima H., Urban J P: The effect of lactate and pH on proteoglycan and protein synthesis rates in the intervertebral disc, Spine, September: 17(9), 1079-1082, 1992). The maximum rate of sulfate incorporation occurs at pH 7.2-6.9. Below pH 6.8, the rate falls steeply. At pH 6.3, the sulfate incorporation rate is only around 32-40% of the rate at pH 72-6.9, Thus, high lactic concentration can (1) slow down the rate of sulfate incorporation to decrease production of the water-retaining sulfated glycosaminoglycans, (2) reduce the swelling pressure or water content within the disc  100 , (3) decrease the capability to sustain compressive loads, and (4) irritate nerve to cause pain. 
     Glucosamine, chondroitin sulfate and dextrose are known to induce proteoglycan biosynthesis and were injected into the discs of patients with chronic low back pain. Fifty-seven percent of the patients showed significant improvement. The patients who showed no improvement were the ones had failed spinal surgery or had spinal stenosis and long-term disability (Klein R G, Eek B C, O&#39;Neill C W, Elin C., Mooney V., Derby R R: Biochemical injection treatment for discogenic low back pain: a pilot study, Spine J., May-June 3(3), 220-226, 2003). Since the anaerobic production of lactic acid may cause acid irritation, buffering agent or antacid should be included in the injection. Other limited disc building ingredients, such as sodium sulfate, proline and amino acids, should also be incorporated in the injection to build sulfated glycosaminoglycans and swelling pressure within the disc. 
     Currently, traditional needle can easily inject into the L3-4 disc or above. The highly problematic L5-S1, L4-L5 discs are shielded between the ilia. Even with highly skillful needle manipulation, needle penetration into L5-S1 or L4-L5 disc is shallow, but the serious nutritional deprivation is within the center of the degenerated disc. In this invention, a rigid needle enters through the pedicle into the vertebral body. Then an elastically curved needle is deployed from the rigid needle to puncture through the calcified endplate into the center of the disc for injection. 
     Resilient straightening of a super elastically curved needle within a rigid needle is described in prior art DE 44 40 346 A1 by Andres Melzer filed on Nov. 14, 1994 and FR 2 586 183-A1 by Olivier Troisier filed on Aug. 19, 1985. The curved needles of this prior art are used to deliver liquid into soft tissue. In order to reach the intervertebral disc, the lengths of the curved and rigid needles must be at least six inches (15.2 cm). There are multiple problems when attempting to puncture the calcified endplate as described in the prior art. Shape memory material for making the curved needle usually is elastic. Nickel-titanium alloy has Young&#39;s modulus of approximately 83 GPa (austenite), 28-41 GPa (martensite). Even if the handles of both the curved  101  and rigid  220  needles are restricted from twisting, the long and elastically curved needle  101  is likely to twist within the lengthy rigid needle  220  during endplate  105  puncturing, as shown in  FIGS. 11 and 12 . As a result, direction of puncture is likely to be deflected and endplate puncture would fail. 
     Furthermore, in the prior art DE 44 40 346 A1 by Andres Melzer filed on Nov. 14, 1994 and FR 2 586 183-A1 by Olivier Troisier filed on Aug. 19, 1985, the sharp tips of their rigid needles are on the concave sides of the curved needles, as shown in  FIG. 15 . When puncturing a hard tissue, such as calcified endplates  105 , the convex sides of the prior art curved needles  101  are unsupported and vulnerable to bending, resulting in failure to puncture through the calcified endplates  105 , as shown in  FIG. 15 . To minimize bending or twisting, the sizes of their curved and rigid needles are required to be large. By increasing the sizes of the curved and rigid needles, friction between the curved and rigid needles greatly increases, making deployment and retrieval of the curved needle very difficult. In addition, a large opening created at the endplate  105  by the large curved needle may cause Schmorl&#39;s nodes, leakage of nucleus pulpous into the vertebral body. 
     This invention contains relevant supports enabling a thin elastically curved needle to puncture the calcified endplate  105  and inject into the disc. Furthermore, the non-round cross-sections of the curved needle  101  and rigid needle  220  are also relevant to prevent curved needle  101  twisting for successful puncturing through the calcified endplate  105  before injecting into the degenerated disc  100 . 
     SUMMARY OF INVENTION 
     The intervertebral disc is avascular. With aging, calcified layers occlude the capillaries at the cartilaginous endplates, reducing diffusion of nutrients and oxygen from capillaries into the avascular disc. Under anaerobic condition, excessive production of lactic acid decreases intradiscal pH and irritates surrounding nerves, causing persistent back pain. Antacid is injected into the painful disc to increase pH and alleviate back pain. 
     In addition, addition, the normalized pH enhances transport of sodium sulfate into the disc to promote biosynthesis of sulfated glycosaminoglycans for retaining additional water to sustain compressive loads upon the disc. As a result, excessive loading and strain on the facet joints are minimized; pain is alleviated. 
     REFERENCE NUMBER 
     
         
           100  Intervertebral disc 
           101  Needle 
           102  Bevel or tapering 
           105  Endplate 
           106  Cartilage 
           107  Capillaries 
           108  Calcified layers 
           112  Blood vessels 
           114  Annular delamination 
           115  Epiphysis 
           116  Penetration marker 
           121  Neuroforamen 
           123  Spinal cord 
           128  Nucleus pulposus 
           129  Facet joint 
           142  Superior articular process 
           143  Inferior articular process 
           159  Vertebral body 
           194  Nerve root 
           195  Posterior longitudinal ligament 
           121  Neuroforamen 
           220  Rigid sleeve or needle 
           224  Puncture 
           230  Dilator 
           268  Lumen of rigid sleeve 
           269  Lumen of rigid needle 
           270  Window of rigid sleeve 
           271  Shape memory extension 
           272  Ramp in lumen of rigid needle 
           276  Syringe 
           278  Pedicle 
           288  Buffering agent, antacid or base 
           289  Filler for intervertebral disc 
           292  Endplate plug 
           374  Lumen of endplate plug 
           375  Static mixer 
           376  Second Filler for disc 
           377  Connector 
           378  Annulus 
       
    
    
    
     
       DESCRIPTION OF THE DRAWINGS 
         FIG. 1  depicts a healthy disc  100  with normal swelling pressure within the nucleus pulposus  128  to support the layers of annulus  378  during compressive loading. 
         FIG. 2  shows a longitudinal view of a spine segment, displaying outward bulging of annulus  378  during compression of the disc  100  between cartilaginous  106  endplates  105 . 
         FIG. 3  shows the calcified layers  108  at the endplates  105 , hindering diffusion of nutrients and oxygen from the vertebral bodies  159  into disc  100 , leading to disc pressure loss and annular delamination  114 . 
         FIG. 4  depicts a degenerated and flattened disc with reduced swelling pressure within the nucleus pulposus  128  and annular delamination  114 . 
         FIG. 5  depicts a syringe  276  filled with buffering agent  288  or filler  289 , connected to an elastically curved needle  101  resiliently straightened within a rigid needle  220  puncturing into the pedicle  278 . 
         FIG. 6  shows insertion of the rigid needle  220  and elastically curved needle  101  into the pedicle  278 . 
         FIG. 7  depicts deployment of the elastic needle  101  from the rigid needle  220 , resuming the curvature and puncturing through the calcified endplate  105  into the disc  100 . 
         FIG. 8  depicts the top view of endplate  105  puncturing using the elastically curved needle  101  into the disc  100 , not shown. 
         FIG. 9  depicts injection of buffering agent  288  or filler  289  from syringe  276  into the disc  100  through the elastically curved needle  100 . 
         FIG. 10  depicts retrieval of the curved needle  101 , resiliently straightened within the rigid needle  220 . 
         FIG. 11  depicts twisting of the curved needle  101  within the rigid sleeve  220  during endplate  105  puncturing. Twisting greatly hinders the capability of endplate  105  puncturing. 
         FIG. 12  shows the circular cross-sections of the curved needle  101  twisting within the rigid needle  220 . 
         FIG. 13  depicts prevention of twisting during endplate  105  puncture by using elliptical cross-sections in curved needle  101  and sleeve  220 . 
         FIG. 14  shows the elliptical cross-sectional view of  FIG. 13 . Twisting or rotation of the elastic needle  101  within the rigid sleeve  220  is significantly limited. 
         FIG. 15  depicts bending or drooping of the unsupported curved needle  101  during endplate  105  puncturing using prior art. Bending hinders endplate  105  puncturing. 
         FIG. 16  shows support from the sharpened tip of the rigid needle  220  beneath the convex side of the curved needle  101  to reduce bending or drooping during endplate  105  puncturing. 
         FIG. 17  depicts an extended distal end of the rigid needle  220  to lengthen the support beneath the convex side of the curved needle  101  during endplate  105  puncturing. 
         FIG. 18  shows a window  270  near the distal end of a sleeve  220  with an elliptical cross-section. The distal portion of the window  270  is slanted or sloped, conforming to the outer wall of the curved needle  101 . 
         FIG. 19  depicts the sharp tip of the elastically curved needle  101  located on the concave side of the curvature for ease of protrusion through the window  270 . 
         FIG. 20  shows support for the convex side of the curved needle  101  by the distal pocket of the window  270  securing the needle  101  to puncture the endplate  105 . 
         FIG. 21  shows a rigid needle  220  with the needle  101  at the securing window  270 . 
         FIG. 22  depicts the elastically curved needle  101  within a curved shape memory extension  271 . Both needle  101  and extension  271  are housed within a rigid sleeve  220 . 
         FIG. 23  shows resilient straightening of the shape memory extension  271  within the rigid sleeve  220 . 
         FIG. 24  shows the convex side support of the needle  101  by the extension  271  without increasing the size of the puncture at the endplate  105 . 
         FIG. 25  shows a sharpened, tubular shape memory extension  271  to support endplate  105  puncturing. 
         FIG. 26  shows a longitudinal cross section of a curved needle  101  with non-uniform outer diameter, supported by a ramp  272  within the lumen  268  of the rigid needle  220 . 
         FIG. 27  shows an endplate plug  292 , slidable over the curved needle  101 , abutting a shape memory extension  271 . 
         FIG. 28  shows advancement of the shape memory extension  271 , pushing the endplate plug  292  to slide along the elastically curved needle  101  into the endplate  105  hole. 
         FIG. 29  shows swelling or sealing of the endplate plug  292  with collapsing lumen  374  occluding the puncture hole at the endplate  105 . 
         FIG. 30  shows the molecular structure of methacrylic acid, a mono component of bone cement, as a filler  289  within the syringe  276  of the curved needle  101 . 
         FIG. 31  shows the molecular structure of the polymerized bone cement, poly-methyl-methacrylate (PMMA), a filler  289  supporting the degenerated disc  100 . 
         FIG. 32  shows a chemical structure of polyethylene glycol, PEG, a filler  289 . 
         FIG. 33  shows a chemical structure of methoxy-PEG, a filler  289 . 
         FIG. 34  shows a chemical structure of methoxy-PEG-amine functional group, a filler  289 . 
         FIG. 35  shows a chemical structure of di-amine functional groups of the PEG, a filler  289 . 
         FIG. 36  shows a chemical structure of methoxy-PEG with a sulfhydro-functional group, a filler  289 . 
         FIG. 37  shows a chemical structure of PEG with di-sulfhydro-functional groups, a filler  289 . 
         FIG. 38  shows a chemical structure of N-hydroxysuccinimide, NHS, functional group on a methoxy-PEG, a filler  289 . 
         FIG. 39  shows a chemical structure of propionate-NHS, functional group on PEG, a filler  289 . 
         FIG. 40  shows a chemical structure of butanoate-NHS functional group on PEG, a filler  289 . 
         FIG. 41  shows a chemical structure of succinimidyl-NHS functional group on PEG, a filler  289 . 
         FIG. 42  shows a chemical structure of maleimide, MAL, functional group on methoxy-PEG, a filler  289 . 
         FIG. 43  shows a chemical structure of a thio-leaving group on PEG, a filler  289 . 
         FIG. 44  shows a chemical structure of MAL and NHS functional groups on PEG, a filler  289 . 
         FIG. 45  shows a chemical structure of di-MAL functional groups on PEG, a filler  289 . 
         FIG. 46  shows a chemical structure of di-MAL functional groups on methoxy-PEG, a filler  289 . 
         FIG. 47  shows a chemical structure of acrylate and NHS functional groups on PEG, a filler  289 . 
         FIG. 48  shows a chemical structure of vinyl sulfone and NHS functional groups on PEG, a filler  289 . 
         FIG. 49  shows a crosslinking reaction between di-NHS-PEG and di-sulfhydro-PEG, fillers  289  within the static mixer  375  and within the disc  100 . 
         FIG. 50  shows a crosslinking reaction between MAL-PEG-NHS and di-sulfhydro-PEG, fillers  289 . 
         FIG. 51  shows a crosslinking reaction between di-MAL-PEG and di-sulfhydro-PEG, fillers  289 . 
         FIG. 52  shows a crosslinking reaction between di-thioester-PEG, di-amine-PEG and di-sulfhydro-PEG, fillers  289 . 
         FIG. 53  shows a crosslinking reaction between vinyl sulfone-PEG-NHS and di-amine-PEG, fillers  289 . 
         FIG. 54  shows two syringes  276  connected to a static mixer  375  for mixing and injecting substances through the curved needle  101  into the degenerated disc  100 . 
     
    
    
     DETAILED DESCRIPTION OF THE EMBODIMENTS 
       FIG. 5  shows rigid needle  220  with a syringe  276  puncturing or entering the pedicle  278  adjacent to a degenerated disc  100 . Pedicle puncturing may require the guidance of fluoroscopy, ultrasound, MRI or other. In addition, trocar puncturing and/or pedicle drilling is preferred prior to rigid needle  220  puncturing. Radiopaque or echogenic coating on the rigid needle  220  and curved needle  101  enhances visual detection and ascertains device position within the vertebral body  159  during endplate  105  puncturing. 
       FIG. 6  shows insertion of the rigid needle  220  and elastically curved needle  101  into the pedicle  278  and partially into the vertebral body  159 . The distal end of the rigid needle  220  is used to support the convex side of the deployed elastically curved needle  101  during calcified endplate  105  puncturing into the disc  100 , as shown in  FIG. 7 .  FIG. 8  shows a top view of the endplate  105  punctured by the supported elastically curved needle  101 . Buffering agent  288  or filler  289  from syringe  276  is injected into the disc  100  through the elastically curved needle  100 , as shown in  FIG. 9 . The curved needle  101  is then retrieved and resiliently straightened within the rigid needle  220 , as shown in  FIG. 10 . The assembly of rigid needle  220 , curved needle  101  and syringe  276  can be rotated 180° to puncture the inferior endplate  105  and inject buffering agent  288  or filler  289  into the inferior degenerated disc  100 . Multiple factors prevent successful endplate puncture. For pedicle  278  entry and disc injection, the minimum length of the elastically curved needle  101  within the rigid needle  220  is about 10 cm, the proper length is about 15 cm. Since the curved needle  101  is elastic, it is likely to twist within the rigid needle  220 , allowing directional shift at the tip of the needle  101  during contact with the calcified endplate  105 . A lengthy curved needle  101  intensifies the twisting problem. The tip of the needle  101  is deflected by the endplate  105  and fails to puncture through the endplate  105 , as shown in  FIG. 11 . A cross-sectional view of the curved needle  101  twisting within the rigid needle  220  is depicted in  FIG. 12 . 
     To prevent twisting between the curved needle  101  and rigid needle/sleeve  220 , the cross sections of both needles are made non-round.  FIG. 13  shows elliptical cross-sections in both curved needle  101  and sleeve  220 . An elliptical cross-sectional view of the curved needle  101  within the rigid needle  220  is depicted in  FIG. 14  to ensure success of endplate  105  puncture. 
     Prior art, DE 44 40 346 A1 by Andres Melzer filed on Nov. 14, 1994 and FR 2 586 183-A1 by Olivier Troisier filed on Aug. 19, 1985, is not designed for puncturing hard surfaces, such as the calcified endplate  105 . In prior art, distal tips of the rigid needles  220  are at the concave sides of their unsupported elastically curved needles  101 , as shown in  FIG. 15 . During calcified endplate  105  puncture using the prior art, bending or drooping of the unsupported curved needle  101  is likely, resulting in failure to puncture the endplate  105 . 
     In this invention, the sharpened tip of the rigid needle  220  beneath the convex side of the curved needle  101  provides support to reduce bending or drooping during endplate  105  puncturing, as shown in  FIG. 16 . To further support the curved needle  101  for injection into the degenerated disc  100 , an extended distal end of the rigid needle  220  lengthens the support beneath the convex side of the curved needle  101  during endplate  105  puncturing, as depicted in  FIG. 17 . A window  270  near the distal end of a rigid sleeve  220  with an elliptical cross-section is shown in  FIG. 18 . The distal portion of the window  270  is slanted or sloped, conforming to the outer wall of the curved needle  101 .  FIG. 19  shows the sharp tip of the elastically curved needle  101  located on the concave side of the curvature to avoid scraping or snagging on the distal portion of the window  270  during deployment of needle  101 . The window  270  with the distal slanted configuration is made to saddle and secure the elastically curved needle  101  from deflecting during endplate  105  puncturing, as shown in  FIG. 20 .  FIG. 21  shows a rigid needle  220  with securing or supporting window  270  for the elastically curved needle  101 . 
     As back pain patients age, calcified endplates  105  harden further. Additional shape memory devices may be essential to support puncturing of the hardened calcified endplate  105  for injection into the degenerated disc  100 .  FIG. 22  depicts the elastically curved needle  101  housed within a curved shape memory extension  271  with a curved distal end.  FIG. 23  shows resilient straightening of both the shape memory extension  271  and curved needle  101  within the rigid sleeve  220 .  FIG. 24  shows support at the convex side of the curved needle  101  by the extension  271 , enabling needle  101  puncture into the calcified endplate  105 . The curvature and inner wall of the curved shape memory extension  271  complement, support and shape-conform to the curvature and outer wall of the curved needle  101 . Since the curved shape memory extension  271  supports only the base or convex side of the needle  101 , the size of the punctured hole at the endplate  105  remains small to minimize loss of hydrostatic pressure or content of the disc  100 .  FIG. 25  shows a sharpened, tubular shape memory extension  271  for penetrating the cancellous bone within the vertebral body  159  and supporting endplate  105  puncturing. 
     The elastically curved needle  101  can be made with non-uniform outer diameter, thinner at the distal end as shown in  FIG. 26 . The thin and sharp distal end of the curved needle  101  is used for puncturing a small opening at the calcified endplate  105 . The thickened body of the curved needle  101  provides strength and support during endplate  105  puncture with crucial support at the base of the curvature near the rigid needle  220 . The lumen  268  of the rigid needle  220  may have a bevel  102  and a double-sided ramp  272 , as shown in  FIG. 26 . The bevel  102  at the distal end of the lumen  268  minimizes friction against the concave side of the curved needle  101  during deployment and retrieval. The double-sided ramp  272  is protruded at the side opposite to the bevel  102  with the distal side in continuation with the sharp tip or extended end of the rigid needle  220 . The proximal side of the ramp  272  or protrusion can be shaped to conform to and support the convex side of the curved needle  101  during endplate  105  puncturing. The ramp  272  can be made with epoxy, solder or other hardened material, then shaped by machining. The ramp  272  can also be created during a molten process to seal the lumen  268  at the distal end. The sealed end is then cut, the ramp  272  and bevel  102  are shaped, and the lumen  268  is re-opened by machining. 
     After injecting buffering agent  288  or disc filler  289  from the syringe  276  into the degenerated disc  100 , leakage into the vertebral body  159  is likely following needle  101  withdrawal. A shape conforming endplate plug  292  is positioned to slide over the curved needle  101 , abutting a shape memory extension  271 , as shown in  FIG. 27 . The plug  292  has a tapered outer wall, thin at the distal end and thick at the proximal end for sealing. After injection of buffering agent  288  or filler  289 , the shape memory extension  271  is advanced to push the plug  292  into the puncture hole at the endplate  105 , as shown in  FIG. 28 . While the curved needle  101  is slightly withdrawn from the endplate  105 , the shape memory extension  271  is further advanced, pushing the plug  292  further into the endplate  105  and collapsing the inner lumen  374  of the soft or shape conforming plug  292 , as shown in  FIG. 29 , to seal the buffering agent  288  or filler  289  within the degenerated disc  100 . The plug  292  can be made with biocompatible material, such as collagen, hyaluronate, alginate, polyethylene glycol, polyurethane, silicon or other. The plug  292  can also swell from hydration to occlude the puncture hole at the endplate  105  and seal the lumen  374  of the plug  292 . 
     Studies indicated that lumbar pain correlates well with high lactate levels and low pH. Antacid, buffering agent or base  288  can be injected from the syringe  276  through the curved needle  101  to neutralize the lactic acid within the degenerative disc  100 , minimize acid irritation and alleviate back pain, as depicted in  FIG. 9 . The antacid, buffering agent or base  288  can be aluminum carbonate, aluminum hydroxide, aluminum oxide, aluminum phosphate, calcium carbonate, calcium hydroxide, calcium phosphate, hydrotalcite, magnesium carbonate, magnesium glycinate, magnesium hydroxide, magnesium oxide, magnesium trisilicate, sodium bicarbonate, sodium carbonate, sodium phosphate or other. 
     Sulfate is an essential ingredient for biosynthesizing the sulfated glycosaminoglycans, responsible for retaining water within the intervertebral disc  100 . Transport of sulfate into the disc  100  is hindered by the acidic pH. After injection of antacid  288 , the normalized pH enhances transport of sodium sulfate into the disc  100  to promote biosynthesis of sulfated glycosaminoglycans necessary for retaining additional water, capable of sustaining compressive loads upon the disc  100 . As a result, excessive loading and strain on the facet joints  129  are minimized and pain is alleviated. In addition, collagen within the annulus  378  of the disc  100  is sensitive to acid hydrolysis. Acidic pH accelerates decomposition and hydrolysis of the degenerating disc  100 . Injection of antacid  288  normalizes pH to preserve peptide bonds in collagen and proteoglycans in disc  100 . 
     Back pain from spinal instability initiated by disc  100  degeneration is very common. Similar to repairing and re-inflating a flat tire of a car, filling and fortifying the degenerated disc  100  minimize instability, lift compressive loads from the facet joints  129  and alleviate back pain. Through minimally invasive punctures using a rigid needle  220  through the pedicle  278  and curved needle  101  through the calcified endplate  105 , disc filler  289  is infused from the syringe  276  to fortify and support the degenerated disc  100 . 
     Methacrylic acid or methyl-methacrylic acid, with molecular structure shown in  FIG. 30 , is a monomer, which can be polymerized into bone cement, poly-methyl-methacrylate (PMMA) as shown in  FIG. 31 . Methacrylic acid, methyl-methacrylic acid can be used as disc fillers  289  to repair, inflate and stabilize degenerated disc  100  with the polymerized PMMA. Polymerization of methyl-methacrylic acids into PMMA is promoted by a base or radical generator. Two syringes  276  connect to the proximal end of a static mixer  375 , the distal end of the mixer  375  connects to the elastically curved needle  101 , as shown in  FIG. 54 . Methyl-methacrylic acid as a filler  289  is filled in one syringe  276 , while the base or radical generator is filled as the second filler  376  in another syringe  276 . The filler  289  and second filler  376  are injected simultaneously into the static mixer  375 , infusing the polymerizing methyl-methacrylic acids into the degenerated disc  100 . As a result, the viscosity of both fillers  289  and  376  increases, preventing leakage through herniated disc  100  or the endplate  105  punctured hole. 
     Polyethylene glycol (PEG) in  FIG. 32  can be a biocompatible filler  289 , capable of retaining water as the sulfated glycosaminoglycans in the nucleus pulposus  128 . Methoxy PEG in  FIG. 33 , methoxy PEG amine in  FIG. 34 , di-amine PEG in  FIG. 35 , methoxy sulfhydro PEG in  FIG. 36 , and di-sulfhydro PEG in  FIG. 37  can be used as fillers  289  and crosslinking derivatives of PEG. The PEG can also be activated for crosslinking reactions with N-hydroxysuccinimide, maleimide, thioester, acrylate and vinyl sulfone with molecular structure of methoxy-PEG-N-hydroxysuccinimide in  FIG. 38 , PEG-propionate-N-hydroxysuccinimide in  FIG. 39 , PEG-butanoate-N-hydroxysuccinimide in  FIG. 40 , PEG-succinimidyl-N-hydroxysuccinimide in  FIG. 41 , methoxy-PEG-maleimide in  FIG. 42 , PEG-thioester in  FIG. 43 , maleimide-PEG-N-hydroxysuccinimide in  FIG. 44 , maleimide-PEG-maleimide in  FIG. 45 , methoxy-PEG-di-maleimide in  FIG. 46 , acrylate-PEG-N-hydroxysuccinimide in  FIG. 47  and vinyl sulfone-PEG-N-hydroxysuccinimide in  FIG. 48 . 
     Di-N-hydroxysuccinimide-PEG as a filler  289  is loaded in a syringe  276 , and di-sulfhydro-PEG as the second filler  376  in pH 5.5-8.0 solution is loaded in another syringe  276 . Both fillers  289  and  376  are mixed within the static mixer  375  and injected through the curved needle  101  into the degenerated disc  100 . The chemical reaction is shown in  FIG. 49 . The rate of crosslinking reaction is pH sensitive, where high pH promotes rapid crosslinking to prevent leakage from herniated disc  100  or the punctured hole at the endplate  105 . As a result, the spinal segment is stabilized and the heavy load on facet joint  129  is partially lifted to alleviate back pain. 
     Similarly, maleimide-PEG-N-hydroxysuccinimide can be a filler  289  in a syringe  276 , while di-sulfhydro-PEG can be the second filler  376  for mixing into a polymerizing PEG to fortify the degenerated disc  100  from within, through the minimally invasive needle puncturing procedure. The chemical reaction is shown in  FIG. 50 . 
     Di-maleimide-PEG and di-sulfhydro-PEG can be another filler  289  and the second filler  376  with chemical reaction shown in  FIG. 51 . Di-sulfhydro-PEG is usually more biocompatible than di-amine-PEG. However, the disc  100  is avascular with little immuno exposure. As a disc filler  289  or  376 , the di-sulfhydro-PEG can probably be interchangeable with di-amine-PEG. The chemical reaction of di-thioester-PEG with di-amine-PEG and di-sulfhydro-PEG is shown in  FIG. 52 . Vinyl-sulfone-PEG as one of the function groups can be used to crosslink with di-amine-PEG as shown in  FIG. 53  to form PEG polymeric filler  289  within the degenerated disc  100  to stabilize the painful segmental instability. Other filler  289 , such as polyurethane, collagen, hyaluronate, silanolate or calcium/barium crosslinked alginate, can also be used. 
     Since nutrient permeability through the calcified endplate  105  diminishes with age, injection of nutrients  288  can significantly increase biosynthesis of chondroitin sulfate and keratan sulfate to retain additional water and regain swelling pressure of the degenerative disc  100 . Unlike the traditional needle used in prior art (Klein R G, Eek B C, O&#39;Neill C W, Elin C., Mooney V., Derby R R: Biochemical injection treatment for discogenic low back pain: a pilot study, Spine J., May-June 3(3), 220-226, 2003), the elastically curved needle  101  can inject nutrients into the centers of L4-5, L5-S1 problematic discs even though they are shielded between the ilia. Nutrients in the syringe  276  through the curved needle  101  can be chondroitin sulfate, keratan sulfate, glucose, glucuronate, galactose, glucosamine, N-acetyl-6-sulfate-D-galactosamine, N-acetyl-6-sulfate-D-glucosamine, proline, glycine, amino acids, thiamine, riboflavin, niacin, niacinamide, pantothenate, pyridoxine, cyanocobalamin, biotin, folate, ascorbate, alpha-tocopheryl, magnesium, selenium, copper, manganese, chromium, molybdenum, vanadium, zinc, silicon, silicone, silicic acid, silanolate, silane, boron, boric acid, sodium sulfate or other. By injecting nutrients, production of sulfated glycosaminoglycans may significantly increase to restore swelling pressure. Restoration of swelling pressure within the nucleus pulposus  128  reinstates the tensile stresses within the collagen fibers of the annulus  378 , thus reducing the inner bulging and shear stresses between the layers of annulus  378 . Similar to a re-inflated tire, disc  100  bulging is reduced and nerve impingement is minimized. The load on the facet joints  129  is also reduced to ease pain, the motion segment is stabilized, and disc  100  space narrowing may cease. The progression of spinal stenosis is halted and/or reversed to ease pain. 
     A growth factor can also be injected through the elastically curved needle  101 , puncturing through the calcified endplate  105  into the disc  100  to promote disc regeneration. Injection of the growth factor, antacid  288 , filler  289  or nutrients through the pedicle  278  using the well supported elastically curved needle  101  minimizes risks and optimizes success of endplate puncture. 
     The rigid needle  101  can be made with stainless steel or other metal or alloy. The elastically curved needle  101  and shape memory extension  271  can be formed with nickel-titanium alloy. The needle  101 , rigid needle  220  and shape memory extension  271  can be coated with lubricant, tissue sealant, analgesic, antibiotic, radiopaque, magnetic and/or echogenic agents. 
     It is to be understood that the present invention is by no means limited to the particular constructions disclosed herein and/or shown in the drawings, but also includes any other modification, changes or equivalents within the scope of the claims. Many features have been listed with particular configurations, curvatures, options, and embodiments. Any one or more of the features described may be added to or combined with any of the other embodiments or other standard devices to create alternate combinations and embodiments. The elastically curved needle  101  can be called the elastic needle  101  or the resilient needle  101 . Some figures show the rigid needle  220  being blunt as a rigid tube  220 . The rigid needle  220  or needle  101  can be generally described in the claims as a sheath with a lumen. Injection of the antacid  288  can also be done with a straight or traditional needle, especially for L3-4 level and above. The vertebral body  159  can be called a vertebra. 
     It should be clear to one skilled in the art that the current embodiments, materials, constructions, methods, tissues or incision sites are not the only uses for which the invention may be used. Different materials, constructions, methods, coating or designs for the injection device can be substituted and used. Nothing in the preceding description should be taken to limit the scope of the present invention. The full scope of the invention is to be determined by the appended claims.